OBJECTIVES: To assess the cost-effectiveness of 18-month treatment with clopidogrel versus aspirin in high-risk patients with a recent history of Ischemic Stroke (IS) or Transient Ischemic Attack (TIA) in four European countries: Belgium, France, Switzerland, and UK. METHODS: We developed a Markov model based on patients with IS or TIA in the previous 90 days (median 15 days) who were treated with clopidogrel in the MATCH trial and followed prospectively for the occurrence of recurrent IS or TIA, myocardial infarction (MI), other cardiovascular death, life threatening bleeding, or major bleeding. The event rates for IS and TIA patients treated with aspirin were derived from a Cochrane review comparing clopidogrel and aspirin by using a relative risk increase (RRI) of 1.11 for serious vascular events (all strokes, MI, cardiovascular deaths). For major bleedings with aspirin vs. clopidogrel, we used a RRI of 1.12 (CAPRIE trial). Death rates for other causes were country specific and adjusted for this population. Lifetime perspective was chosen and discount rates were applied according to the local guidelines. RESULTS: Eighteen-month treatment with clopidogrel compared to aspirin was associated with a gain in quality adjusted life years (QALY) ranging from 31 years / 1000 patients in the UK to 36 years / 1000 patients in Belgium. The incremental cost per patient varied from 487€ in UK to 724€ in Belgium and the cost per QALY was 20,111€ in Belgium, 18,882€ in France, 15,620€ in Switzerland, and 15,713€ in UK. Sensitivity analyses showed that all results were robust under various assumptions. CONCLUSION: Consistent results are found across the four countries with incremental cost-effectiveness ratio below the acceptable thresholds, demonstrating that clopidogrel compared to aspirin is always cost-effective in the studied population.