Clopidogrel is a thienopyridine that acts by inhibiting the adenosine diphosphate-dependent activation of platelets. It has proven efficacy in two general categories: long-term secondary prophylaxis in populations with existing vascular disease, and of limited duration following cardiovascular events or procedures. Clopidogrel may be used alone or in combination with aspirin, depending on the indication. The cost-effectiveness of clopidogrel varies with the indication, the population in which it is used, the risk of future events faced by that population and whether it is combined with aspirin. This article will review existing data on the cost-effectiveness of clopidogrel for each indication with a particular focus on these four criteria.