OBJECTIVES: The CAPRIE study has demonstrated an 8.7% relative risk reduction (RRR) for atherothrombotic events (vascular death, myocardial infarction, ischemic stroke) compared with aspirin (ASA) in patients with symptomatic atherothrombotic disease. The objective of this study was to assess the cost-effectiveness of clopidogrel relative to ASA for secondary prevention of ischemic events in the Netherlands. METHODS: The cost-effectiveness, in terms of cost per life-year saved, was determined with a Markov model in which patients were divided according to vascular events and time from last event. Effectiveness data were derived from the CAPRIE study; long-term outcomes were based on epidemiological estimates concerning age specific event rates and case fatality rates. Direct costs were updated from previous studies, indirect costs were disregarded due to the age of the patients. Discount rate was 4% for both costs and effects. RESULTS: Compared with aspirin, using event-specific risk reductions, 1-year treatment with clopidogrel costs €743 more with a gain in life-years and quality adjusted life-years (QALY's) of 0.033 and 0.043 respectively. Using a constant RRR of 8.7%, the results were consistent providing a cost per life-year saved of €19.462 and a cost per QALY of €15.779. Sensitivity analyses revealed that uncertainties surrounding the outcomes are mainly driven by the expected effectiveness, most notably when defining sub-groups. The higher the risk for events, the better the cost-effectiveness ratio. In comparison to no treatment (ASA intolerance or previous failure) clopidogrel is expected to combine gain in effectiveness (0.158 life years, 0.210 QALY's) with savings (€332 per patient). CONCLUSIONS: Clopidogrel is a dominant strategy in patients not eligible for treatment with ASA. The cost effectiveness is within an acceptable range when compared with ASA, especially in high-risk patients.