OBJECTIVES: To estimate the long and short term costs and effects of clopidogrel versus ASA in the prevention of ischemic events (MI, IS, VD) in three high-risk CAPRIE sub-populations: 1) patients with a history of coronary artery bypass grafting; 2) patients with a history of ischemic events; 3) patients with multiple vascular territory involvement. In addition, an analysis for ASA intolerant patients in the general CAPRIE population was performed. METHODS: A Markov model consisting of 24 health states that combined clinical, epidemiological and cost data was used to assess the cost and effects of clopidogrel in comparison to ASA. Only in the ASA intolerant patients, clopidogrel was compared to no treatment. RESULTS: The comparison of clopidogrel with ASA in the high-risk CAPRIE sub-groups resulted in cost-effectiveness ratios of DKK25,445 (3,424€)/LYG, DKK 51,198 (6,881€)/LYG, and DKK55,503 (7,460€)/LYG for 1) patients with a history of coronary artery bypass grafting; 2) patients with a history of ischemic events; and 3) patients with multiple vascular territory involvement respectively. The comparison of clopidogrel to no treatment for the ASA intolerant patients resulted in DKK 3093 (416€)/LYG. Cost-effectiveness ratios of this order are generally considered acceptable in modern Western societies. Internal and external validity have been tested and were ascertained. CONCLUSIONS: Clopidogrel may be considered a cost-effective treatment for the prevention of subsequent ischemic events in high-risk patient populations and in the general CAPRIE-population with ASA intolerance in Denmark. Extensive sensitivity analyses confirmed that these results were stable over the entire range of assumptions.