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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

  December 22, 2009

Delivered via EDGAR

Securities
and Exchange Commission

Division of Corporation Finance

100
First Street, N.E.

Mail
Stop 4720

Washington,
DC 20549

  Attn:

  Jim B. Rosenberg, Senior Assistant Chief Accountant

  Kei Ino, Staff Accountant

  Mark Brunhofer, Senior Staff Accountant

  Mike Rosenthall, Staff Attorney

  Jennifer Riegel, Staff Attorney

  Re:

  Vertex Pharmaceuticals Incorporated

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

  Form 10-Q for the Quarterly Period Ended
  March 31, 2009

  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 October 23,
2009 to Kenneth S. Boger, Senior Vice President and General Counsel of the
Company.  This letter supplements the
Company’s letter to the SEC dated November 18, 2009.  The comments from the Comment Letter are
reproduced below together with the Company’s responses to those comments.

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

Compensation Discussion and Analysis

2008 Compensation Decisions for
Performance-Based Elements, page 29

Comment 1:

We note your response to our prior comment 4.  However, your response does not appear to
address our concerns.  To the extent that
your four high-level goals are more specifically defined than the disclosure in
your document, they should be more specifically described.  For example, one of the goals is to “meet or
exceed timelines in clinical, regulatory, quality, manufacturing and commercial
operations toward a successful launch of telaprevir.”  If the goals, as communicated to your
executives, are more

specific as to these timelines, these timelines
should be described.  If you believe that
a more specific disclosure of these goals would be competitively harmful,
please provide us with an analysis supporting your belief.  The analysis should identify the information
that you believe would cause competitive harm, describe the competitive harm
you are likely to experience if the information is disclosed and explain why
this information is not material to investors.
We will not be in a position to assess the likelihood of competitive
harm if we do not know what the specific goals are.  Please be advised that you may request
confidential treatment for portions of your response pursuant to Rule 83.  Please provide proposed disclosure for your
2010 proxy statement.

Additionally, comment 4 indicated that when
information relating to targets and goals is not provided on the basis that
disclosure is not material and is likely to cause competitive harm, you must
discuss how difficult it will be for the executive or how likely it will be for
the company to achieve the undisclosed goals or targets.  Your response directs our attention to the
disclosure relating to the level of achievement which is not the same as a
discussion of the level of difficulty to achieve the stated goals and
targets.  If you continue to believe that
your goals and targets quality for confidential treatment, please discuss the
level of difficulty related to the undisclosed goal(s) or target(s).

Response:

The Company does not expect that any of the
performance targets material to the board of director’s compensation decisions
for 2009 performance will involve confidential trade secrets or confidential
commercial or financial information, and accordingly, the Company expects to
disclose all such material performance targets in its 2010 Proxy
Statement.  While the Company’s board of
directors maintains discretion to consider all factors it deems relevant in
establishing the Company’s performance rating in any year, for 2009 the Company
expects that its board of directors will evaluate the Company’s performance and
progress with respect to each of the following:

·                                          Meet or exceed mission-critical milestones toward a successful launch of
telaprevir in 2011; strengthen HCV franchise

·                                          Maintain financial strength

·                                          Build organizational strength

·                                          Demonstrate increase in portfolio value beyond HCV

After 2009 year-end, the Company expects that the
board of directors will evaluate the Company’s overall performance in each of
these areas in light of relevant facts and circumstances, and that the board of
directors will weight some areas more heavily than others.  In particular, the Company expects that the
board of directors will place greater weight on the first two categories
(telaprevir/HCV and maintain financial strength).

The Company expects that the board of directors’
evaluation in the first area (telaprevir/HCV) will  include a review of the company’s performance
in (a) assuring telaprevir launch and chemistry, manufacturing and
controls (CMC) readiness; (b) building the new drug application (NDA)
dossier for a timely filing (to support a 2011 launch); (c) ensuring that
product inventory will be in place; (d) building a commercial
infrastructure; (e) developing a life cycle plan for telaprevir; and (f) securing
rights to a STAT-C compound (such as VX-222) and initiating

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development of a combination therapy with
telaprevir.  Similarly, the Company
expects that the board of directors will consider factors applicable to each of
the other three categories.

While the Company expects the board of directors
will assign an overall weight to each category, it expects that the board of
directors will reach this decision on the basis of a general facts and
circumstances analysis of factors such as those listed above, and will not
specifically weight each factor.  On the
basis of that assessment, the board of directors will assign the Company a
performance rating and establish the size of the bonus pool.  The Company expects that its 2010 proxy statement
will include disclosure of the performance rating, together with detail about
each of the factors that were material to the board’s assessment.

Since there may be considerable variability from
year to year in the types of performance targets considered by the board of
directors, it may be that in future years these objectives will involve
information that remains confidential beyond the period during which
compensation decisions are made.  For
example, in 2009, the Company has been focused on conducting late-stage
clinical trials of its hepatitis C protease inhibitor, telaprevir.  For each pharmaceutical drug candidate, the
competitive landscape and development pathway, including timelines, are more
uncertain in the earlier stages and become clearer as the asset advances
through development.  By 2009, the
potential projected launch in 2011 for telaprevir was well-established and was
disclosed. In contrast, in 2008, the nature of likely competition from
telaprevir’s nearest competitors, both in terms of product profile and
time-to-market, was much less clear, and the Company’s goals included a
confidential contingency plan (including timelines for certain activities) for
different possible scenarios, the disclosure of which would have provided an
advantage to competitors and competitive harm to the Company.  The Company’s performance objectives in the
future with respect to earlier stage drug candidates may include competitive
information of this sort.  In addition,
once the Company has a commercial product, the board of directors may establish
performance objectives that include confidential commercial information such as
market share or pricing information.  For
its Proxy Statement in years beyond 2010, the Company undertakes to omit only
those material factors for which it has a reasoned basis to conclude that
disclosure would cause competitive harm to the Company, to discuss how
difficult it will be to achieve the undisclosed factors, if any, and to
supplementally provide both the confidential performance target and a
competitive harm analysis to the Staff upon request.

Form 10-Q for the Quarterly Period Ended March 31,
2009

Preliminary Allocation of Assets and
Liabilities, page 18

Comment 2:

We acknowledge your response to comment seven
(a).  Although the nature, timing and
estimated costs of the efforts to complete the development of VX-222 and VX-759
are subject to risks and uncertainties, we do not understand why meaningful
estimates are not available when it would appear that these costs are a significant
component of the cash flow assumptions inherent in your fair value assessment
of these projects.  Please revise your
disclosure to provide the nature, timing and estimated costs to complete these
projects as utilized in your fair value assessment.

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Response 2:

The Company hereby supplements its response to
Comment 2 contained in its November 18, 2009 letter to the SEC as follows:

The Company will augment its disclosure regarding the acquisition of
ViroChem in the Company’s Annual Report on Form 10-K for the year ending December 31,
2009, to be updated if circumstances dictate, as follows:

“Projections
of the duration and cost of non-clinical studies and clinical trials vary
significantly over the life of a project depending on developments in the
program over time, but in order to estimate the fair value on the acquisition
date we made the following assumptions from the perspective of a market
participant regarding the potential timing and costs to develop VX-222 and/or
VX-759.  We assumed if a drug candidate
were successfully developed in the United States it would take approximately
five to nine years from the date of the acquisition in order to obtain such
approval.  In addition, for the valuation,
we assumed an estimate of cost from acquisition to launch to develop a drug
candidate that was within a range of $400 million to $700 million”.

Comment 3

We acknowledge your response to comment seven
(c).  Please address the following
additional comments:

·                                          You indicate that you did
not ascribe value to ViroChem’s other preclinical programs and other
technologies because market participants would be unlikely to ascribe value to
them.  Please tell us how many other
preclinical programs and other technologies you acquired from ViroChem and the
associated treatment indications.

·                                          It appears that you based
the $7.2 million fair value assigned to the VCH-286 intangible asset based on
the development costs incurred through the acquisition date.  Please demonstrate to us how the value
assigned is consistent with that derived by a market participant and how it
complies with the guidance in paragraph 33 of SFAS 141R.  Please revise your disclosure accordingly.

Response 3

The
Company hereby supplements its response to Comment 3 contained in its November 18,
2009 letter to the SEC as follows:

The
“other technologies” that were identified by the Company are patents and patent
applications unrelated to the ViroChem drug development projects and candidates
that we valued separately.  The Company
determined that market participants would not ascribe any value to these
patents and patent applications because the Company did not identify any
commercial potential for the covered subject matter.  The determination that there was no
commercial potential for the subject matter was based on a variety of reasons
including the patents or patent applications related to (i) drug candidates for
which development had been terminated as a result of adverse safety or efficacy
data and (ii) early research projects that did not result in the identification
of a drug candidate.

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

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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.

Please
contact me at 617-444-6417 in the event that you have any questions or concerns
with respect to this matter.  In the
event that I am not available, please contact my colleague, Valerie Andrews, at
617-444-6227.

  Very
  truly yours,

  /s/
  Kenneth S. Boger

  Kenneth
  S. Boger

  Senior
  Vice President and General Counsel

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