SECURITIES PURCHASE AGREEMENT dated as of September 18, 2009 by and among

Exhibit 10.1

SECURITIES PURCHASE AGREEMENT

dated as of September 18, 2009

by and among

OPKO HEALTH, INC.

AND

THE PURCHASERS SET FORTH ON
THE SIGNATURE PAGES HERETO

SECURITIES PURCHASE AGREEMENT

     THIS SECURITIES PURCHASE AGREEMENT (this “ Agreement ”) is dated effective as of September 18, 2009, by and between OPKO Health, Inc. (the “ Company ”), a corporation organized under the laws of the State of Delaware, with its principal offices at 4400 Biscayne Boulevard, Miami, Florida 33137 (the “ Principal Office ”), and the purchasers whose names and addresses are set forth on the signature pages hereto (the “ Purchasers ”). Certain capitalized terms used but not defined herein shall have the respective meanings set forth on Schedule 1 attached hereto.

     IN CONSIDERATION of the mutual covenants contained in this Agreement, and intending to be legally bound hereby, the Company and the Purchasers agree as follows:

     SECTION 1. Authorization of Sale of the Shares . Subject to the terms and conditions of this Agreement, and the filing with the Secretary of State of the State of Delaware of the Certificate of Designation of the Powers, Preferences and Relative, Participating, Optional and Other Special Rights of the 8.0% Series D Cumulative Convertible Preferred Stock, and Qualifications, Limitations and Restrictions Thereof, substantially in the form attached hereto as Exhibit A (the “ Certificate of Designation ”), the Company has authorized the issuance and sale to the Purchasers in a private placement of an aggregate of 1,209,677 shares of 8.0% Series D Cumulative Convertible Preferred Stock, par value $0.01 per share, of the Company (each, a “ Share ” and collectively, the “Shares”), and, in connection therewith warrants (the “ Warrants ”) to purchase an aggregate of 3,024,196 shares of the Common Stock, par value $ 0.01 per share, of the Company (the “ Common Stock ”).

     SECTION 2. Agreement to Sell and Purchase the Shares . Subject to the terms and conditions of this Agreement, at the Closing (as defined in Section 3), the Company shall issue and sell to each Purchaser, and such Purchaser shall buy from the Company, the number of Shares and Warrants set forth on such Purchaser’s signature page hereto for an aggregate purchase price equal to the number of Shares purchased by such Purchaser multiplied by the per-Share purchase price of $24.80 (the “ Purchase Price ”). The sum of the aggregate purchase prices paid by all Purchasers pursuant to the terms of this Agreement is $29,999,989.60, the product of (x) 1,209,677 and (y) $24.80.

     SECTION 3. Closing

          3.1 Delivery of the Shares at the Closing . The completion of the purchase and sale of the Shares (the “ Closing ”) shall occur at the Principal Office as soon as practicable and as agreed to by the parties hereto, on or around September 23, 2009, or on such other date or at such different location as the parties hereto shall mutually agree, but not prior to the date on which the Closing Conditions (as defined below) have been satisfied or waived (the “ Closing Date ”).

          3.2 Closing Deliverables . At the Closing, or as promptly thereafter as is practicable, the Company shall deliver to each Purchaser (x) one or more stock certificates registered in the name of such Purchaser, or, if so indicated on such Purchaser’s Stock Certificate Questionnaire, the form of which is attached hereto as Appendix I (the “ Stock Certificate Questionnaire ”), in such other name(s) as designated by such Purchaser, evidencing the number of Shares set forth on such Purchaser’s signature page attached hereto, each bearing a restrictive legend, substantially in the form set forth in Section 6.3, and (y) a Warrant Certificate, in substantially the form of Exhibit B attached hereto (each, a “ Warrant Certificate ”), evidencing the number of Warrants set forth on the investor signature page hereto executed by Purchaser.

          3.3 Conditions to the Company’s Obligations . The Company’s obligation to complete the sale of the Shares and the Warrants at the Closing is subject to the fulfillment, at or prior to the Closing, of each of the following conditions, unless otherwise waived (“ Company Closing Conditions ”):

               (a) receipt by the Company of immediately available funds in the full amount of the aggregate purchase price for all Shares being purchased at the Closing;

               (b) each of the representations and warranties of each Purchaser set forth in Section 5 shall be true and correct on the date of the Closing; and

               (c) each Purchaser shall have performed and complied with all covenants, agreements and obligations contained in this Agreement that are required to be performed or complied with by such Purchaser on or prior to the Closing.

          3.4 Conditions to Purchasers’ Obligations . Each Purchaser’s obligation to purchase the Shares and Warrants at the Closing is subject to the fulfillment, at or prior to the Closing, of each of the following conditions, unless otherwise waived (“ Purchaser Closing Conditions ” and, together with the Company Closing Conditions, the “ Closing Conditions ”):

               (a) each of the representations and warranties of the Company set forth in Section 4 that is qualified by materiality or material adverse effect or words of similar effect shall be accurate in all respects on the Closing Date (except to the extent any such representations and warranties expressly relate to a specific date, in which case such representations and warranties shall be accurate as of such date), and each of the representations and warranties of the Company set forth in Section 4 that is not so qualified shall be accurate in all material respects as of the Closing Date (except to the extent such representations and warranties expressly relate to a specific date, in which case such representations and warranties shall be accurate in all material respects as of such date);

               (b) the Company shall have performed and complied with all covenants, agreements and obligations contained in this Agreement that are required to be performed or complied with by the Company on or before the Closing; and

               (c) the Certificate of Designation shall have been filed with, and accepted for filing by, the Secretary of State of the State of Delaware.

     SECTION 4. Representations, Warranties and Covenants of the Company . The Company hereby represents and warrants to the Purchasers as follows:

          4.1 Issuance of Shares . The Company has taken all necessary corporate action to authorize the execution, delivery and performance of this Agreement and the Company’s issuance and sale of the Shares and Warrants. The Shares, when issued and delivered and paid for as provided herein, will be duly authorized, validly issued, fully paid and nonassessable and will be issued free and clear of any Encumbrances (other than as arising under applicable securities laws or this Agreement). Assuming the accuracy of the representations and warranties of the Purchasers set forth in Section 5 of this Agreement, the Shares will be issued in compliance with all applicable federal and state securities laws.

          4.2 Organization and Qualification . The Company is a corporation duly organized, validly existing and in good standing under the laws of the State of Delaware and has the requisite corporate power and authority to own, lease and operate its properties and to carry on its business as it is now being conducted and is duly qualified to do business in any other jurisdiction by virtue of the nature of the businesses conducted by it or the ownership or leasing of its properties, except where the failure to be so qualified will not, when taken together with all other such failures, have a Material Adverse Effect on the Company.

          4.3 Charter and Bylaws . The Company’s Charter and Bylaws, as amended or restated to date, as filed with the SEC, are a complete and correct copy of such documents as in effect on the date hereof.

          4.4 Capitalization . As of September 18, 2009, the Company has (i) authorized 500,000,000 shares of Common Stock, 253,632,889 shares of which are issued and outstanding, (ii) authorized 4,000,000 shares of Series A Preferred Stock, $0.01 par value per share, 932,667 shares of which are issued and outstanding, (iii) authorized 500,000 shares of Series C Preferred Stock, $0.01 par value per share, 0 shares of which are issued and outstanding; and (iv) 2,000,000 shares of Series D Preferred Stock (“Series D Preferred Stock”), 0 shares of which are issued and outstanding. All such outstanding shares of Common Stock and Preferred Stock have been duly authorized and are validly issued, fully paid and nonassessable. Except as disclosed in the SEC Documents, as of the date hereof, there are no outstanding options, warrants, rights to subscribe for, calls or commitments of any character whatsoever relating to, or securities or rights convertible into or exchangeable for, shares of any class of capital stock of the Company, or agreements, understandings or arrangements to which the Company is a party, or by which the Company is or may be bound, to issue additional shares of its capital stock or options, warrants or rights to subscribe for, calls or commitment of any character whatsoever relating to, or securities or rights convertible into or exchangeable for, any shares of any class of its capital stock.

          4.5 Authorization, Enforceability and Related Matters . (i) The Company has full right, power, authority and capacity to enter into this Agreement and to consummate the transactions contemplated hereby and has taken all necessary corporate action to authorize the execution, delivery and performance of this Agreement; (ii) the making and performance of this Agreement by the Company and the consummation by the Company of the transactions contemplated herein will not violate any provision of the Company’s Charter or Bylaws or, except to the extent that it would not have a Material Adverse Effect on the Company or adversely affect the Company’s ability to consummate the transactions contemplated hereby, conflict with, result in the breach or violation of, or constitute, either by itself or upon notice or the passage of time or both, a default under any material agreement, mortgage, deed of trust, lease, franchise, license, indenture, permit or other instrument to which the Company is a party, or any statute or any authorization, judgment, decree, order, rule or regulation of any court or any regulatory body, administrative agency or other governmental agency or body applicable to the Company; (iii) no consent, approval, authorization or other order of any court, regulatory body, administrative agency or other governmental agency or body is required in respect of the Company’s execution and delivery of this Agreement or the consummation by the Company of the transactions contemplated by this Agreement; (iv) upon the execution and mutual delivery of this Agreement by the parties hereto, this Agreement shall constitute a legal, valid and binding obligation of the Company, enforceable against the Company in accordance with its terms, except as enforceability may be limited by applicable bankruptcy, insolvency, reorganization, moratorium or other laws of general application relating to the enforcement of creditor’s rights and the application of equitable principles relating to the availability of remedies, and except as rights to indemnity or contribution may be limited by federal or state securities laws or the public policy underlying such laws; and (v) there is not in effect any order enjoining or restraining the Company from entering into or engaging in any of the transactions contemplated by this Agreement.

          4.6 Brokers or Finders . No broker, investment banker, financial advisor or other individual, corporation, general or limited partnership, limited liability company, firm, joint venture, association, enterprise, joint securities company, trust, unincorporated organization or other person or entity is entitled to any broker’s, finder’s, financial advisor’s or other similar fee or commission in connection with the transactions contemplated by this Agreement based upon arrangements made by or on behalf of the Company or any of its Affiliate.

          4.7 SEC Documents . The Company has made available to the Purchasers true and complete copies of all SEC Documents. As of their respective dates (or if amended, as of the date of the last amendment filed prior to the date hereof), the SEC Documents complied in all material respects with the requirements of the 1934 Act, and rules and regulations of the SEC promulgated thereunder, and the SEC Documents did not contain any untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading.

          4.8 Company Financial Statements . The financial statements, together with any notes thereto, included in the Company’s Annual Report on Form 10-K as filed with the SEC on March 16, 2009 and the Company’s Quarterly Report on Form 10-Q as filed with the SEC on August 7, 2009 fairly present in all material respects, on the basis stated therein and on the date thereof, the financial position of the Company at the respective dates therein specified and its results of operations and cash flows for the periods then ended. Such statements and related notes have been prepared in accordance with generally accepted accounting principles in the United States (“ GAAP ”) applied on a consistent basis except as expressly noted therein and subject in the case of the unaudited financial statements to year-end adjustments.

          4.9 Material Changes; Undisclosed Events, Liabilities or Developments . Since June 30, 2009, except as disclosed in any SEC Document filed subsequent to June 30, 2009 and prior to the date hereof: (i) there has been no event, occurrence or development that has had or that could reasonably be expected to result in a Material Adverse Effect; (ii) the Company has not incurred any material liabilities (contingent or otherwise) other than (A) trade payables and accrued expenses incurred in the ordinary course of business consistent with past practice and (B) liabilities not required to be reflected in the Company’s financial statements pursuant to GAAP; (iii) the Company has not altered its method of accounting; (iv) the Company has not declared or made any dividend or distribution of cash or other property to its stockholders or purchased, redeemed or made any agreements to purchase or redeem any shares of its capital stock; and (v) the Company has not issued any equity securities to any of its officers, directors or Affiliates. As of the date hereof, except for the issuance of the Shares contemplated by this Agreement, no event, liability or development has occurred or exists with respect to the Company or its subsidiaries or their respective business, properties, operations or financial condition that is required to be disclosed by the Company under applicable securities laws.

          4.10 Full Disclosure . No representation or warranty made by the Company in this Agreement contains any untrue statement of a material fact, or omits to state a material fact necessary to make the statements contained herein not misleading.

     SECTION 5. Representations, Warranties and Covenants of the Purchasers . Each Purchaser severally, and not jointly with any other Purchaser, represents and warrants to the Company that:

          5.1 Experience . (i) Such Purchaser is knowledgeable, sophisticated and experienced in financial and business matters, and is making, and is qualified to make, decisions with respect to investments in shares representing an investment decision like that involved in the purchase of the Shares, including investments in securities issued by the Company and/or comparable entities, has the ability to bear the economic risks of an investment in the Shares and has had the opportunity to request, receive, review and consider all information it deems relevant in making an informed decision to purchase the Shares; (ii) such Purchaser is acquiring the number of Shares set forth on such Purchaser’s signature page attached hereto for its own account, solely for investment and with no present intention to distribute any of such Shares and is subject to no arrangement or understanding with any other persons regarding the distribution of such Shares; (iii) such Purchaser will not, directly or indirectly, offer, sell, pledge, transfer or otherwise dispose of (or solicit any offers to buy, purchase or otherwise acquire or take a pledge of) any of the Shares, except in compliance with the Securities Act of 1933, as amended (the “ Securities Act ”), and the rules and regulations promulgated thereunder (the “ Rules and Regulations ”) and any applicable state securities laws; (iv) such Purchaser has, in connection with its decision to purchase the number of Shares set forth on such Purchaser’s signature page attached hereto, relied solely upon the representations and warranties of the Company contained in this Agreement; (v) such Purchaser has had an opportunity to discuss this investment with representatives of the Company and ask questions of them; and (vi) such Purchaser is either a “qualified institutional buyer” as defined by Rule 144A promulgated under the Securities Act or an “accredited investor” as defined by Rule 501(a) of Regulation D promulgated under the Securities Act.

          5.2 Reliance on Exemptions . Such Purchaser understands that the Warrants, the Shares, and the Common Stock issuable upon conversion of the Shares (the “ Conversion Shares ” and, together with the Shares and the Warrants, the “ Securities ”) are being offered and sold to in reliance upon specific exemptions from the registration requirements of the Securities Act and state securities laws and that the Company is relying upon the truth and accuracy of, and the Purchaser’s compliance with, the representations, warranties, covenants, agreements, acknowledgments and understandings of such Purchaser contained in this Agreement in order to determine the availability of such exemptions and the eligibility of the Purchaser to acquire the Securities.

          5.3 Confidentiality . Such Purchaser understands that this Agreement, the information contained in all materials provided to the Purchase