The role of aspirin in the secondary prevention of ischaemic events is being challenged. CAPRIE, a blinded multicenter randomized trial of over 19,000 patients followed for 1-3 years, assessed the effect of clopidogrel in the secondary prevention of major vascular events. Patients with a recent myocardial infarction, stroke or peripheral arterial disease were randomized to treatment with clopidogrel or aspirin. Clopidogrel was associated with a statistically significant, overall 8.7%, relative reduction in the risk of ischaemic events, but the direction and size of the effect was not homogeneous with respect to three predefined clinical subgroups. Clopidogrel may be slightly better in preventing major ischaemic events in high-risk patients, but the results of CAPRIE suggest that there is room for doubt. It remains to be seen whether treatment with clopidogrel is cost-effective compared with aspirin. However, aspirin may still be of value in the early treatment of acute stroke. IST was a 20,000 patient, randomized, open-label study of aspirin plus heparin or neither in patients with acute ischaemic stroke that should be treated in 48 hours. There was a small but statistically nonsignificant reduction in mortality and disability at 6 months for patients allocated to early treatment with aspirin compared with those who were scheduled to avoid aspirin in the first 2 weeks after the stroke. Similar results were seen in CAST, a double-blind trial of aspirin vs. placebo in patients with suspected ischaemic stroke treated within 48 hours. A meta-analysis of the results of IST, CAST and MAST-I showed a statistically significant effect of early aspirin treatment. The role of aspirin in the treatment of acute stroke within 48 hours appears to be established.