BACKGROUND: The authors reviewed various recommendations and practices for cost-effectiveness analysis. They also performed a PubMed search for clopidogrel and cost-effectiveness from 2004 to early 2008 to obtain original analyses published in English to look for possible associations of assumptions and conclusions with reported pharmaceutical support. RESULTS:. Inclusion of incident cases and truncation at a sensible follow-up time more appropriately reflect the burden to be assumed by third-party payers. Extending the time horizon too far runs the risk of decreasing any relation with future reality. Parsimony cannot justify simplifications that omit relevant issues such as noncoronary costs, which worsen the calculated cost-effectiveness ratio of clopidogrel by 5% to 27%. The choice of the population to be analyzed has a major effect on cost-effectiveness: pharmaceutically sponsored studies published between 2004 and early 2008 focused on high-risk patients and have routinely shown more favorable cost-effectiveness ratios for clopidogrel than studies without pharmaceutical support. CONCLUSION:. Any entity hoping to make the cost-effectiveness ratio of clopidogrel look more favorable would prefer the isolated, cohort approach and limit the analysis to high-risk patients most likely to benefit from it. This approach ignores the reality of medical policies and does not address the most relevant questions regarding the optimum use of clopidogrel.