OBJECTIVES: The Clopidogrel for the Reduction of Events During Observation (CREDO) trial showed that clopidogrel loading prior to percutaneous coronary intervention (PCI) with one-year treatment after PCI reduced the combined risk of death, myocardial infarction (MI) or stroke. The purpose of this study was to evaluate the economic impact of clopidogrel based on CREDO in Switzerland, Belgium, Italy, and France. METHODS: We used clinical outcomes and resource use from CREDO combined with external survival data to assess the long-term cost-effectiveness of clopidogrel. A total of 2116 patients with coronary artery disease were randomized to clopidogrel loading before PCI plus one year therapy (n=1053) vs. 28 days clopidogrel followed by placebo (n=1063). All patients received clopidogrel day zero to 28. In all, 89 (8.45%) patients in the treatment arm and 122 (11.48%) in the placebo group had an event (RRR 26.9%, 95% CI 3.9%-44.4%). Hospitalizations were assigned a Diagnostic Related Group (DRG) through a DRG grouper. Unit costs were developed in each country and applied to all patients of the CREDO study. Lost life expectancy associated with death, MI and stoke was estimated from Saskatchewan data and discounted 3%. Cost effectiveness was expressed as the cost per event avoided and as cost per Life year saved (LYS). RESULTS: The cost effectiveness of one year use of clopidogrel in addition to a clopidogrel loading strategy prior to PCI vs. placebo ranges from 15,765€ to 26,074€ /event prevented. The cost per LYS is 2483€/LYS in Belgium, 2502€ /LYS in France; 2552€ /LYS in Italy; 2659€ /LYS in Switzerland based on Saskatchewan projection. CONCLUSION: Clopidogrel used prior to PCI and for one year thereafter is a cost effective strategy. Consistent results are found in the four countries studied.