INDENTURE

Exhibit 4.1

HEALTH MANAGEMENT ASSOCIATES, INC.

3.75% Convertible Senior Subordinated Notes due 2028

INDENTURE

Dated as of May 21, 2008

U.S. BANK, NATIONAL ASSOCIATION

TRUSTEE

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INDENTURE dated as of May 21, 2008 between HEALTH MANAGEMENT ASSOCIATES, INC., a Delaware corporation (the “ Company ”), and U.S. BANK, NATIONAL ASSOCIATION, a national banking association, (in such capacity, together with its successors in trust, the “ Trustee ”).

Each party agrees as follows for the benefit of the other party and for the equal and ratable benefit of the Holders of the Company’s 3.75% Convertible Senior Subordinated Notes due 2028 (the “ Securities ”):

ARTICLE 1

D EFINITIONS A ND I NCORPORATION B Y R EFERENCE

Section 1.01 . Definitions.

“ 144A Global Security ” means a permanent Global Security in the form of the Security attached hereto as Exhibit A-1, and that is deposited with and registered in the name of the Depositary, representing Securities sold in reliance on Rule 144A under the Securities Act.

“ Additional Interest ” means all amounts, if any, payable pursuant to Section 4.07 and Section 6.02 hereof.

“ Affiliate ” of any specified person means any other person directly or indirectly controlling or controlled by or under direct or indirect common control with such specified person. For purposes of this definition, “ control ” when used with respect to any specified person means the power to direct or cause the direction of the management and policies of such person, directly or indirectly, whether through the ownership of voting securities, by contract or otherwise; and the terms “ controlling ” and “ controlled ” have meanings correlative to the foregoing.

“ Applicable Conversion Rate” means, for each $1,000 principal amount of Securities to be converted, the sum of the Daily Conversion Rate Fractions for each VWAP Trading Day during the related Observation Period for such Securities.

“ Applicable Procedures ” means, with respect to any transfer or transaction involving a Global Security or beneficial interest therein, the rules and procedures of the Depositary for such Security, in each case to the extent applicable to such transaction and as in effect from time to time.

“ Base Conversion Price ” on any day means, for each $1,000 principal amount of Securities, a dollar amount (initially, approximately $11.76) equal to $1,000 divided by the Base Conversion Rate, as may be adjusted pursuant to Section 11.06 (and without, for the avoidance of doubt, giving effect to any adjustment to the Base Conversion Rate pursuant to Section 11.02).

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“ Base Conversion Rate ” means, for each $1,000 principal amount of Securities, 85.0340 shares of the Class A Common Stock, subject to adjustment as set forth herein.

“ Beneficial Owner ” shall be determined in accordance with Rule 13d-3 promulgated by the Commission under the Exchange Act.

“ Bid Solicitation Agent ” means initially the Company or any agent the Company may appoint in the future, including the Trustee, to solicit a Trading Price for the Securities as may be required pursuant to this Indenture.

“ Board of Directors ” means either the board of directors of the Company or any duly authorized committee of such board.

“ Business Day ” means each day of the year other than a Saturday or a Sunday on which banking institutions are not required or authorized to close in the City of New York.

“ Capital Lease Obligation ” means, at the time any determination thereof is to be made, the amount of the liability in respect of a capital lease that would at such time be required to be capitalized on a balance sheet in accordance with GAAP.

“ Capital Stock ” for any Person means any and all shares, interests, rights to purchase, warrants, options, participations or other equivalents of or interests in (however designated) stock issued by that Person.

“ Class A Common Stock ” means shares of class A common stock, par value $0.01 per share, as it exists on the date of this Indenture and any shares of any class or classes of Capital Stock of the Company resulting from any reclassification or reclassifications thereof and which have no preference in respect of dividends or of amounts payable in the event of any voluntary or involuntary liquidation, dissolution or winding-up of the Company and which are not subject to redemption by the Company; provided, however, that if at any time there shall be more than one such resulting class, the shares of each such class then so issuable on conversion of Securities shall be substantially in the proportion which the total number of shares of such class resulting from all such reclassifications bears to the total number of shares of all such classes resulting from all such reclassifications.

“ Closing Date ” means the date of this Indenture.

“ Common Equity ” of any Person means Capital Stock of such Person that is generally entitled to (1) vote in the election of directors of such Person or (2) if such Person is not a corporation, vote or otherwise participate in the selection of the governing body, partners, managers or others that will control the management or policies of such Person.

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“ Company ” means the party named as the “ Company ” in the first paragraph of this Indenture until a successor replaces it pursuant to the applicable provisions of this Indenture and, thereafter, shall mean such successor. The foregoing sentence shall likewise apply to any subsequent successor or successors.

“ Company Request ” or “ Company Order ” means a written request or order signed in the name of the Company by any two Officers.

“ Continuing Director ” means a director who either was a member of the Company’s board of directors on the date of this Indenture or who becomes a director of the Company subsequent to such date and whose election, or nomination for election by the Company’s stockholders, is duly approved by a majority of the Continuing Directors on the board of directors at the time of such approval, either by a specific vote or by approval of the proxy statement issued by the Company on behalf of the entire board of directors of the Company in which such individual is named as nominee for director.

“ Controlled ” means ownership or control of more than 50% of the voting power of such entity.

“ Corporate Trust Office ” means the principal office of the Trustee at which at any time its corporate trust business shall be administered, which office at the date hereof is located at 200 South Biscayne Blvd. Suite 1870, Miami, FL 33131, or such other address as the Trustee may designate from time to time by notice to the Holders and the Company, or the principal corporate trust office of any successor Trustee (or such other address as a successor Trustee may designate from time to time by notice to the Holders and the Company).

“ Daily Conversion Rate Fraction ” means, for any Securities to be converted and each Daily VWAP Trading Day of the related Observation Period for such Securities, a number of shares of Class A Common Stock determined as follows:

(i) if the Daily VWAP on such day is less than or equal to the Base Conversion Price on such day, the Daily Conversion Rate Fraction for such day shall be the Base Conversion Rate in effect on such day divided by 20; and

(ii) if the Daily VWAP on such day is greater than the Base Conversion Price on such day, the Daily Conversion Rate Fraction for such day shall be equal to the following fraction: