THIRD AMENDMENT TO STOCKHOLDERS AGREEMENT

Exhibit 10.1

THIRD AMENDMENT TO STOCKHOLDERS’ AGREEMENT

     THIS AGREEMENT is made and entered into effective as of the 15 ^th day of July, 2008, by and between Spheris Holding III, Inc. (hereinafter referred to as the “Company”), Spheris Investment LLC, the Warburg Investors and the TowerBrook Investors (f/k/a Soros Investors). Capitalized terms used herein without definition elsewhere in this Amendment are defined in Section 17 of the Stockholders’ Agreement (as defined below).

     WHEREAS, the Company, the Warburg Investors, the TowerBrook Investors and Spheris Investment LLC have previously entered into a Stockholders’ Agreement, dated November 5, 2004 as amended by that certain First Amendment to Stockholders’ Agreement, dated August 17, 2006, and that certain Second Amendment to Stockholders’ Agreement, dated May 2, 2007 (the “Stockholders’ Agreement”);

     WHEREAS, the Company, Spheris Investment LLC, the Warburg Investors and the TowerBrook Investors wish to modify and amend the Stockholders’ Agreement according to the terms set forth herein.

     NOW, THEREFORE, in consideration of the premises and for good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Company, the Warburg Investors and the TowerBrook Investors do hereby agree as follows:

     1. Paragraph 3.1 of the Stockholders’ Agreement is hereby deleted in its entirety and amended and restated as follows:

     “As of the date hereof, the Board of Directors of the Company (the “Board”) shall consist of Jonathan Bilzin, Wayne Smith, Neal Moszkowski, Steven Simpson, Michael King, Robert Z. Hensley and John A. Kane. From and after the date hereof, the Investors and the Company shall take all action within their respective power, including but not limited to, the voting of all Shares Owned by them, required to cause the Board to consist of no more than nine (9) members, and at all times throughout the term of this Agreement, to include:

(a) at the option of the Warburg Investors, for as long as the Warburg Investors Own at least twenty percent (20%) of the Common Stock Owned by Investors, two (2) members designated by Warburg Pincus and, for as long as the Warburg Investors Own at least five percent (5%) but less than twenty percent (20%) of the Common Stock Owned by Investors, one (1) member designated by Warburg Pincus (such members referred to herein as “Warburg Directors” and each a “Warburg Director”);

(b) for as long as the TowerBrook Investors Own at least twenty percent (20%) of the Common Stock Owned by Investors, two (2) members designated by the TowerBrook Investors and, for as long as the TowerBrook Investors Own at least five percent (5%) but less than twenty percent (20%) of the Common Stock Owned by Investors, one (1)

member designated by the TowerBrook Investors (such members referred to herein as “TowerBrook Directors” and each a “TowerBrook Director”);

(c) one (1) member of management who shall be the Chief Executive Officer of the Company then in office (the “Management Director”);

(d) four (4) independent members selected by the Majority Warburg Investors and the Majority TowerBrook Investors (such members referred to herein as “Independent Directors” and each an “Independent Director”).

     The parties hereto acknowledge that the four representatives to be designated by the Warburg Investors and the TowerBrook Investors are the directors that the holders of Preferred Stock are entitled to elect under the Restated Certificate. The parties hereto further acknowledge that as of the date hereof there are no Warburg Directors, the TowerBrook Directors shall be Jonathan Bilzin and Neal Moszkowski, the Management Director shall be Steven Simpson and the Independent Directors shall be Wayne Smith, Robert Z. Hensley, John A. Kane and Michael King. In addition, subject to the ownership requirements set forth in paragraphs (a) and (b) of this Section 3.1, the Warburg Investors, on the one hand, and the TowerBrook Investors, on the other hand, shall be entitled to designate an equal number of directors.”.

     2. Paragraph 3.3 of the Stockholders’ Agreement is hereby amended as follows:

     (i) by inserting the words “, at the option of the Majority Warburg Investors,” after the words “any such committee shall have,” and

     (ii) by inserting the words “, at the option of the Majority TowerBrook Investors,” after the words “so long as the Warburg Investors are entitled to elect at least one member of the Board and”.