Background: Little is known about the quality of studies evaluated by the United States Food & Drug Administration (FDA) for medical device approval. The most rigorous FDA review process, for novel and high-risk devices, is called Premarket Approval (PMA). Objectives: To assess studies examined by the FDA for all cardiovascular device PMAs between 2000-2007 for the presence of study modifications or post-hoc primary endpoint interpretations. Methods: The summary of safety and effectiveness data for all cardiovascular device PMAs was downloaded and any study modifications or post-hoc primary endpoint interpretations were recorded by one author and confirmed by two other authors. Results: Of the 71 cardiovascular PMAs between 2000-2007 containing a study with at least one primary endpoint, 15 (21%) had some form of study modification or post-hoc primary endpoint interpretation. In eight of these PMAs, a study did not meet at least one pre-specified primary endpoint, but the device was approved on the basis of a post-hoc data review. Pre-specified statistical analyses were changed after study initiation in three PMAs. Two PMAs were approved on qualitative merits rather than quantitative data after the FDA deemed the study characteristics no longer applicable at the time of review. Pre-specified controls were changed in two PMAs. In one PMA each, study design was modified after study initiation, a primary endpoint was redefined after study initiation, or new patients were added to a study after completion of initial enrolment. Conclusions: The most rigorous FDA review process includes numerous forms of post-hoc study modification and primary endpoint re-interpretation. More consistent requirements for pre-specified clinical trial outcomes will help improve the quality of the approval process and ensure that medical devices are safe and effective.