OBJECTIVES: To determine the incremental cost per life year saved (ICLYS) of clopidogrel versus ASA in secondary prevention of ischemic stroke (IS), myocardial infarction (MI), or vascular death (VD) in 2 high risk sub-groups of the CAPRIE trial (patients with prior IS or MI to index event, and atherothrombotic patients treated for hypercholesterolemia and/or with diabetes) in Belgium. METHODS: A Markov model designed with 7 clinical states calculated ICLYS as the cost needed to achieve an extra life year with clopidogrel compared to ASA. The model combined rates of clinical outcomes calculated from the CAPRIE database and survival data derived from the Saskatchewan database. The costing of events, including acute care and follow-up, was performed using official data (DRG systems), tariffs and/or charges (physicians fees, examinations, lab tests), divided in acute costs and costs per subsequent 6 month follow-up periods. The economic analysis was performed from the health care system perspective using only direct medical costs for 2-year treatment. A discount rate of 3% was applied to costs and lifetime effects. RESULTS: In first subgroup (prior MI or IS), 27 additional atherothrombotic events (14 MI, 12 IS, 1VD) were avoided per 1000 patients treated with clopidogrel versus ASA with a gain in survival of 119 years. In second subgroup (hypercholesterolemia and/or diabetes), 28 additional atherothrombotic events (14 MI, 8 IS, 6VD) were avoided with a gain in survival of 130 years per 1000 patients. The incremental cost of the clopidogrel arm compared to ASA was €702 in first group and €771 in second group. The ICLYS was very similar in the 2 subgroups: €5900 and €5930 respectively. Results were robust under a wide variation of key parameters. CONCLUSION: Clopidogrel as an alternative to ASA is a cost-effective strategy in secondary prevention of ischemic events for high-risk atherothrombotic patients.