Background The CURE study demonstrated that clopidogrel prevents a range of ischaemic cardiovascular events in patients with Acute Coronary Syndromes (unstable angina or non-ST-segment elevation MI). Design We undertook an economic analysis of the use of clopidogrel in the UK, USA, Sweden, France and Canada based on the CURE study. Methods The costs of hospitalization, study drug and other medications were calculated, based on resource utilization for all patients in CURE. Unit costs were obtained for all resource items for each country, and are reported in local currencies in 2001 prices. Results While hospitalization costs were lower in the clopidogrel group, when the acquisition cost of clopidogrel for 9 months is included, the average cost per patient is higher in the clopidogrel group than the placebo group in all countries [difference in costs (with 95% CI) UK £208 (119, 297), US$451 (58, 845), SKr 2571 (728, 4412), Fr &U20AC;325 (85, 565), C$161 (−185, 506)]. The absolute reduction in the number of total primary events was 2.0%, resulting in an incremental cost-effectiveness ratio (ICER) of £10,366 in the UK, $22,484 in the USA, SKr 127,951 in Sweden, &U20AC;16,186 in France, and C$7973 in Canada per primary event avoided with clopidogrel. Conclusions Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months. Nevertheless, the cost-effectiveness is in a range comparable to other therapies currently utilized for acute coronary syndromes.