Objective: The REACH Registry shows that the rate of death, myocardial infarctions (MI) and ischaemic strokes (IS) increase as the number of symptomatic arterial disease locations increases. A cost-utility analysis was undertaken comparing two years of clopidogrel treatment with aspirin treatment for patients with a previous history of MI, who then sustain an IS or a peripheral arterial disease (PAD) event. These patients are referred to as ‘high-risk'. Methods: A model was constructed to simulate hypothetical ‘high-risk' patients. The time horizon was that of patient lifetime with only direct medical costs considered. Health states included were vascular death, non-fatal IS events and non-fatal MI events. The risk of future events in the ‘high-risk' group compared with patients who had sustained a single event (MI, IS or PAD) was calculated from the CAPRIE trial and showed an 81% increase. This ratio was applied to previously published risks of vascular death, non-fatal IS and non-fatal MI for UK patients with a single event to calculate the event rates for ‘high-risk' patients. The relative risks (and 95% confidence intervals) of clopidogrel compared with aspirin in ‘high-risk' patients in the CAPRIE trial were 0.87 (0.63 – 1.19), 0.83 (0.60 – 1.15) and 0.53 (0.32 – 0.86) for vascular death, non-fatal IS and non-fatal MI events respectively. Costs and utilities associated with events were taken from literature reviews and were discounted at 3.5% per annum. Probabilistic sensitivity analyses were undertaken. Results: The mean cost per QALY for clopidogrel compared with aspirin was £5443 (95% confidence interval £2332 to dominated). The probability of the cost per QALY being below £20,000, a significant threshold for cost-effectiveness in the UK, was 79%. Conclusion: The model suggests that, in patients with a previous MI event and a subsequent IS or PAD event, clopidogrel can be considered cost-effective compared with aspirin in terms of current UK thresholds.