In the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, clopidogrel showed a statistically significant superiority over aspirin in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients with symptomatic atherosclerosis. More recently, post-hoc analysis of the data also showed that repeat hospitalization for ischaemic or bleeding events was decreased with clopidogrel compared with aspirin. Complementary analyses show that the benefit of clopidogrel over aspirin is amplified in a large population at very high risk of further atherothrombotic events (diabetics, patients with high cholesterol, and patients with previous manifestations of atherothrombosis). A potential clinically useful advantage of clopidogrel is its low propensity for adverse interaction with angiotensin-converting enzyme (ACE) inhibitors, contrary to what may be seen with aspirin, as observed in a post-hoc CAPRIE analysis. The putative aspirin-ACE inhibitor interaction is being tested prospectively in the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial - a randomized comparison of warfarin, clopidogrel and aspirin in patients with chronic heart failure. The good gastrointestinal tolerance of clopidogrel seen in CAPRIE has been further demonstrated in a study in healthy volunteers where there was a markedly lower gastroduodenal erosion score after 8 days' administration of clopidogrel 75 mg/day compared with aspirin 325 mg/day (p < 0.001). Following the positive findings obtained with clopidogrel plus aspirin in the Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS) trial, other studies of clopidogrel plus aspirin have been initiated or are planned. These include Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH), a randomized comparison of clopidogrel plus aspirin versus clopidogrel in high-risk patients with recent stroke or transient ischaemic attack.