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  VERTEX PHARMACEUTICALS
  INCORPORATED

  130 WAVERLY STREET ·
  CAMBRIDGE, MA 02139-4242

  TEL. 617.444.6100 · FAX
  617.444.7117

  http://www.vrtx.com

  March 31,
  2010

Delivered via EDGAR

Securities
and Exchange Commission
 Division of Corporation Finance

100
First Street, N.E.

Mail
Stop 4720

Washington,
DC 20549

  Attn:

  Jeffrey P. Riedler, Assistant Director

  Mike Rosenthall, Staff Attorney

  Re:

  Vertex Pharmaceuticals Incorporated

  Form 10-K for the Period Ended
  December 31, 2008

  Definitive Proxy Statement on Schedule 14A filed
  April 8, 2009

  File No. 000-19319

Ladies
and Gentlemen:

The purpose of this letter is to respond to the
comments provided by the staff (the “Staff”) of the Securities and
Exchange Commission (the “SEC”) to Vertex Pharmaceuticals Incorporated
(the “Company”) in a letter dated February 19, 2010 to the
Company.  The comments from the comment
letter are reproduced below together with the Company’s responses to those
comments.

Schedule 14A

Compensation Discussion and Analysis

2008 Compensation Decisions for
Performance-Based Elements, page 29

Comment 1:

We note that your response
to our prior comment 1 indicates you expect that the board of directors will
evaluate corporate performance with regard to the factors indicated but that
the factors considered is at the discretion of the board of directors.  Please confirm that your next proxy statement
will include the following:

·                                          Confirmation that no
corporate performance targets are set at the beginning of each fiscal year to
be used at the end of the fiscal year to gauge corporate or executive
performance;

·                                          The analysis performed by
the board of directors used to determine performance at the end of each fiscal
year; and

·                                          How the performance
evaluation was used to determine the amount of bonuses awarded to each named
executive officer based on the extent of achievement determined by the board.

Response 1:

As the Company discussed with a representative of
the Staff, the Company’s board of directors sets goals for Company’s
performance early in the year and uses these goals to evaluate the Company’s
performance at the beginning of the following year (while retaining discretion
to consider all factors it deems relevant to such performance evaluation). The
four goals set during 2009 and used in February 2010 to determine the
Company’s 2009 rating were to:  meet or exceed
mission critical milestones toward a successful launch of telaprevir, and
strengthen our HCV franchise; maintain financial strength; build organizational
strength; and demonstrate increase in portfolio value beyond HCV.  The Company confirms that in its 2010
Definitive Proxy Statement (i) it will disclose these goals, (ii) it
will describe the analysis performed by the board of directors to determine
performance at the end of the year and (iii) it will describe how the
performance evaluation was used to determine the amount of the bonuses and
equity awards awarded to each executive officer for 2009 performance.  The disclosure regarding the Company’s 2009
compensation decisions for performance-based elements will be substantially as
set forth in Exhibit A and Exhibit B to this letter.

In
addition, the Company confirms that in its 2010 definitive proxy statement (i) it
will disclose that 50% of the shares subject to both the Company’s 2007 PARS
awards and the Company’s 2008 PARS awards will vest if the Company’s common
stock achieves and maintains a market price of $60.00 per share and (ii) it
will add disclosure regarding the reason that Dr. Boger’s salary was
increased to the midpoint of the range for CEOs in our comparator company
group.

The Company hereby confirms that in future filings
the Company will enhance its overall disclosures by complying with the comments
provided by the SEC in the manner set forth in the responses above, subject in
all cases, to any changes with respect to the facts underlying the Company’s
disclosures.

The Company acknowledges that:

1)                                      the Company is
responsible for the adequacy and accuracy of the disclosure in its filings;

2)                                      Staff comments
or changes to disclosure in response to Staff comments do not foreclose the
Commission from taking any action with respect to the filing; and

3)                                      the Company may
not assert Staff comments as a defense in any proceeding initiated by the
Commission or any person under the federal securities laws of the United
States.

2

Please contact me at 617-444-6227 in the event that
you have any questions or concerns with respect to this matter.

  Very truly yours,

  /s/ Valerie L. Andrews

  Valerie L. Andrews

  Deputy General Counsel

3

Exhibit A

Disclosure in Compensation
Discussion and Analysis

2009 Compensation Decisions for Performance-Based
Elements.

Company
Rating—Our board of directors evaluated overall 2009 company performance
against four goals that it established early in 2009:

·                                          meet or exceed
mission critical milestones toward a successful launch of telaprevir, and
strengthen our HCV franchise;

·                                          maintain
financial strength;

·                                          build
organizational strength; and

·                                          demonstrate
increase in portfolio value beyond HCV.

The MDCC recommended and the
board determined that our company performance rating for 2009 was “Leading.”  The board set the company performance factor
for the 2009 executive bonus pool at 150%, which is the highest possible
performance factor under our program. This rating was based on our having
achieved or exceeded all four of the pre-determined goals. In reaching this
determination, the board considered the following:

·                  Telaprevir
and HCV Franchise—We advanced toward a successful future launch of
telaprevir by successfully completing patient enrollment and dosing in all
Phase 3 telaprevir clinical trials, demonstrating readiness for commercial
supply of telaprevir and building inventory for commercial launch, conducting
appropriate value analyses for telaprevir, executing on the telaprevir
life-cycle plan through BID dosing and HCV/HIV co-infection clinical trials,
and we successfully strengthened our HCV franchise by securing rights to
VX-222, consistent with our strategy of investigating “STAT-C” (oral
combination) therapy for HCV infection, through the acquisition of Virochem
Pharma, Inc.

·                  Financial
Strength—We demonstrated financial strength by finishing the
2009 fiscal year with approximately $1.285 billion in cash, cash equivalents
and marketable securities, including cash realized from restructuring our
Mitsubishi Tanabe license arrangement and through financial transactions
relating to our rights to future milestone payments under our Janssen
Pharmaceutica collaboration agreement, and managing our net cash loss to
approximately $510 million.

·                  Organizational
strength—We successfully managed a series of leadership
transitions in our executive ranks, involving our CEO, Chief Commercial
Officer, Chief Medical Officer and head of Global Research &
Development; established a 5-year corporate vision and long-range plan, and
effectively expanded our capabilities in the areas of research, development and
pharmaceutical commercialization.

·                  Portfolio
Value—We demonstrated increased value in our non-HCV programs, including
progression of our CF program through a Phase 3 clinical program for VX-770, a
Phase 2 clinical trial of VX-809 and definition of a regulatory pathway for a
CF corrector/potentiator combination; preparing our JAK-3 inhibitor, VX-509,
for Phase 2 clinical investigation in patients with RA; submitting a
satisfactory protocol for Phase 2 clinical trials of VX-765 in epilepsy; and
continuing research productivity by producing several early-stage molecules
suitable for further study.

Although the directors discuss and analyze our
performance as a group, each director makes his or her own judgment about which
factors are important, and how to weight those factors in reaching a conclusion.

Individual
Ratings for Named Executive Officers—The MDCC recommends to the
board for approval both a results-based and a values-based rating for each of
our executives.  The results-based rating
recommendation for each named executive is the combined result of the committee
members’ observations and review of the officer’s role in the accomplishment of
the corporate goals, and factors and recommendations provided to the MDCC by
our chief executive officer, Mr. Emmens, made on the basis of Mr. Emmens’
independent assessment of each executive officer’s performance in 2009.  The MDCC and Mr. Emmens discussed the
recommendations at length, on both an individual-by-individual basis, and on a
comparative basis.   Upon completion of
these discussions, the MDCC finalized its recommendation for the results-based
rating for each executive, taking into account Mr. Emmens’
recommendations, factors considered in the discussions, and the opinions of
committee members based on the executive’s contributions and the members’
interactions with the executive.  When
considering the more subjective values-based rating, the MDCC also discussed Mr. Emmens’
recommendations, giving them greater weight than for the results-based rating,
because the values-based rating is pertinent to the executive’s daily
interactions in carrying out his or her duties, and the MDCC believes that in
his role as CEO, Mr. Emmens has greater visibility than the committee
members into the quality of these interactions.

Mr. Emmens also
discussed his own performance in 2009 with the MDCC. Mr. Emmens noted that
Vertex’s performance rating was the highest possible under our system, due to
our exceptional performance across all aspects of the business. The board of
directors determined that Mr. Emmens’ rating similarly should be at the
highest possible level, and rated Mr. Emmens’ 2009 performance as “leading.”
For values-based behavior, the board of directors believes that Mr. Emmens
is an exceptional leader who exhibits exemplary values-based behavior, and
accordingly, assigned Mr. Emmens a values-based rating of “exemplary
demonstration.”

The MDCC recommended
results-based and values-based ratings for each of Dr. Mueller, Mr. Sachdev
and Mr. Smith to the board of directors. Ms. Wysenski joined us in December 2009,
and thus was ineligible for year-end bonus or equity awards on account of 2009
performance. The MDCC recommended and the board of directors approved a
results-based rating of “leading” for Dr. Mueller, because in addition to
consistent and excellent research productivity, Dr. Mueller oversaw a year
of extraordinary success for the pharmaceutical operations and the chemistry,
manufacturing and controls programs, particularly for the telaprevir
Phase 3 clinical trial and launch preparation. He also successfully took
on additional

responsibility for our development organization
mid-year.  Dr. Mueller was rated “exemplary”
for values-based behavior in his leadership of our entire scientific
organization.   Similarly, the MDCC’s
recommendation for Mr. Sachdev’s performance rating of “leading,” based in
part on a number of initiatives in the public sector that have the potential to
increase the value of our HCV franchise, was adopted by the board.  Mr. Smith’s organization, which includes
finance and accounting, real estate, operations, information systems and
strategic communications, also performed at a high level in supporting
achievement of the corporate objectives detailed above, particularly in
accessing over $1 billion through debt and equity offerings and other
financial transactions, causing the MDCC to recommend and the board to approve
a results-based rating of “leading” for Mr. Smith.  With respect to values-based evaluation, the
MDCC recommended that each of Mr. Smith and Mr. Sachdev be rated “living
the values” because they demonstrated strong values-based behavior.

Based on the foregoing, the
named executive officers earned the following performance ratings and
individual performance factors on account of 2009 performance.

  Results—Based

  Rating

  Values—Based

  Rating

  2009
  Overall

  Performance

  Rating

  Individual

  Performance

  Factor

  Matthew W. Emmens

  Leading

  Exemplary Demonstration

  Leading/Exemplary

  150

  %

  Ian F. Smith

  Leading

  Living the Values

  Leading

  145

  %

  Peter Mueller

  Leading

  Exemplary Demonstration

  Leading/Exemplary

  150

  %

  Amit Sachdev

  Leading

  Living the Values

  Leading

  145

  %

Annual
Cash Bonus and Equity Awards—The annual cash bonuses and
annual equity awards for 2009 resulting from the company and individual
performance ratings are set forth in the tables under the headings Compensation and Equity Tables—Summary Compensation
Table—Non-Equity Incentive Plan Compensation—Cash Bonus and Compensation and Equity Tables—Summary Compensation
Table—Stock Awards and Options Awards.

Exhibit B

Disclosure Referenced in
Compensation Discussion and Analysis

and Presented under

Compensation and Equity Tables

Stock Awards and Options Awards

The total equity awards made
to each of the named executives on account of 2009 performance are as
follows.  Pursuant to applicable rules only
the grant date value of the stock options awarded in July 2009 are
included in the table above and the grant date values of the awards granted in February 2010
will be included as 2010 compensation.

  Individual

  Performance

  Rating

  Stock
  Options

  Awarded in

  July 2009

  Stock
  Options

  Awarded in

  February 2010

  Total Stock

  Options

  Awarded for 2009

  Performance

  Restricted

  Stock Awarded

  in February 2010

  for 2009 Performance

  Matthew W. Emmens

  Leading/Exemplary

  n/a

  354,000

  354,000

  47,201

  Ian F. Smith

  Leading

  36,250

  54,375

  90,625

  12,084

  Peter Mueller

  Leading/Exemplary

  36,250

  72,500

  108,750

  14,501

  Amit Sachdev

  Leading

  30,500

  45,750

  76,250

  10,166

Non-Equity
Incentive Plan Compensation—Cash Bonus

The amounts set forth under
the caption “Non-Equity Incentive Plan Compensation” represent cash bonuses for
2009, 2008 and 2007 performance, each of which was paid in the first quarter of
the next year.   The cash bonus awards to
the named executive officers for 2009 performance were determined as follows:

  2009 Base

  Salary

  Level

  Individual

  Incentive

  Target

  2009

  Target

  Bonus

  Company

  Performance

  Factor

  Individual

  Performance

  Factor

  2009

  Bonus

  Matthew W. Emmens

  $

  1,100,000

  115

  %

  $

  1,265,000

  150

  %

  150

  %

  $

  2,846,251

  Ian F. Smith

  $

  463,500

  40

  %

  $

  185,400

  150

  %

  145

  %

  $

  403,245

  Peter Mueller

  $

  550,000

  40

  %

  $

  220,000

  150

  %

  150

  %

  $

  495,000

  Amit Sachdev

  $

  365,907

  35

  %

  $

  128,067

  150

  %

  145

  %

  $

  278,547