OBJECTIVES: To assess the effectiveness of clopidogrel in addition to aspirin versus aspirin alone after acute coronary syndrome (ACS) in an Australian context. METHODS: A Markov model was constructed to simulate the onset of major cardiovascular events (composite of myocardial infarction, ischemic stroke and cardiovascular death), major bleeding events and non-cardiovascular death in a representative cohort of 1000 subjects experiencing ACS. In the first year post ACS, underlying risks of events were drawn from the nationwide Australian Acute Coronary Syndromes Prospective Audit (ACACIA) registry (n=2553). In subsequent years, risks from Australian participants of the Reduction in Atherothrombosis for Continued Health (REACH) registry (n=2567) were used. Decision analysis compared the two interventions and follow-up was simulated for ten years. Relative risks of cardiovascular and bleeding events associated with clopidogrel were drawn from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, and assumed to be sustained as long as subjects remained on treatment. Uncertainty analyses were undertaken via Monte Carlo simulation. RESULTS: The modeled outcomes from the simulated follow-up of 1000 subjects in the ten year model were major CV events, major bleeding events and deaths. There were fewer CV events and deaths in the clopidogrel arm but more bleeding events than aspirin. The number needed to treat (NNT) to avoid a major CV event was 14 (9-29); to avoid a death was 33 (14-207). Overall, there were 8413 life years gained in clopidogrel compared with 8191 in aspirin alone. CONCLUSIONS: In the simulated cohort, the addition of clopidogrel to aspirin represents a highly effective strategy for the secondary prevention of death and cardiovascular events following ACS. Although there is a small increase in bleeding in the simulated cohort, the net effect remains a significant prevention of cardiovascular events, saving of lives and years of life gained.