The objective of the analysis is to estimate the long-term costs and effects of clopidogrel versus aspirin in the secondary prevention of ischemic events in patients with a history of more than one atherothrombotic event in Belgium. The following high-risk subpopulations within the CAPRIE trial were analysed: patients with a history of myocardial infarction (MI) or ischemic stroke (IS) prior to the event qualifying for enrolment and patients with prior multiple vascular territory involvement. A Markov model that combined clinical, epidemiological and cost data was used. The base case scenario was based on a treatment duration of 5 years reflecting the long-term use of clopidogrel. A lifelong time horizon was taken, by applying life expectancy data based on the Saskatchewan database. Belgian cost estimates were derived from publicly available sources and literature. Long-term clopidogrel treatment compared to aspirin in patients with a history of MI or IS prior to the event qualifying for enrolment is associated with an incremental cost-effectiveness ratio (ICER) ranging between 2.730 Euro per life year gained (LYG) for the first year of treatment and 8.000 Euro/LYG for a treatment duration of 5 years. In patients with prior multiple vascular territory involvement the ICER of clopidogrel compared to aspirin lays between 3.110 Euro and 5.750 Euro/LYG for the respective treatment durations. Use of clopidogrel for the prevention of subsequent cardiovascular events in patients with a history of more than one ischemic event is associated with favourable ICERs, independently of the presumed treatment duration. Sensitivity analyses varying life expectancy, efficacy of clopidogrel, costs of events and cost of adverse events and discount rates demonstrated the robustness of the results.