BACKGROUND: Antiplatelet therapy plays a central role in the prevention of atherothrombotic events. Both acetylsalicylic acid (aspirin) and clopidogrel have been shown to reduce the risk of recurrent cardiovascular events in various subgroups of patients with vascular disease. OBJECTIVE: To estimate the cost effectiveness of clopidogrel versus aspirin in Sweden for the prevention of atherothrombotic events based on CAPRIE trial data. The focus of this study is on two high-risk subpopulations: (i) patients with pre-existing symptomatic atherosclerotic disease; and (ii) patients with polyvascular disease. METHODS: A Markov model combining clinical, epidemiological and cost data was used to assess the economic value of clopidogrel compared with aspirin during a patient's lifetime. A societal perspective was used, with costs stated in Swedish kronor (SEK), year 2007 values. For the first 2 years, the clinical input for the model was based on the relevant subpopulations in the CAPRIE trial. Thereafter, transition probabilities were extrapolated, taking account of increased risks related to age and to a history of events. Cost effectiveness of 2 years of therapy is presented as cost per life-year gained (LYG) and as cost per QALY. Univariate and multivariate sensitivity analyses were performed to investigate robustness of results. RESULTS: For patients resembling the total CAPRIE population, who were treated with clopidogrel, the expected cost per LYG was SEK217,806 and the cost per QALY was estimated at SEK169,154. For the high-risk CAPRIE subpopulations, costs per QALY were lowest for patients with pre-existing symptomatic atherosclerotic disease (SEK38,153). Using a 'willingness-to-pay' perspective indicated that treatment with clopidogrel instead of aspirin in high-risk patients is associated with a high probability for cost effectiveness; 81% using a threshold of SEK100,000 per QALY and 98% using a threshold of SEK500,000 per QALY. Overall, the results appeared to be robust over the sensitivity analyses performed. CONCLUSION: When considering the cost-effectiveness categorization as proposed by the Swedish National Board of Health and Welfare, clopidogrel appears to be associated with costs per QALY that range from intermediate in the total CAPRIE population to low in high-risk atherosclerotic patients.