Aspirin is effective in reducing vascular outcomes in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death and 15% for vascular mortality. It is probable that moderate and high-dose aspirin are similar in efficacy, but this has not been proven in stroke prevention. Low-dose aspirin, such as 30 or 75 mg a day, may be equally as effective. Complications of high-dose aspirin are more frequent than with low doses. Four cerebrovascular randomized trials evaluating sulfinpyrazone versus placebo, and three trials evaluating sulfinpyrazone versus aspirin, showed more events in the sulfinpyrazone than in the aspirin and placebo groups. One small trial compared dipyridamole to placebo in patients with cerebrovascular disease and there were no differences in outcomes in the two groups. No other studies have compared dipyridamole alone to placebo or aspirin. The European Stroke Prevention Study II is in progress and is comparing (1) aspirin 25 mg twice daily, (2) dipyridamole 200 mg twice daily, (3) aspirin 25 mg + dipyridamole 200 mg twice daily and (4) placebo. The Ticlopidine Aspirin Stroke Study showed, in the 1st year, a 42% risk reduction for stroke and death by the efficacy analysis and a 47% risk reduction for stroke and stroke death. The superiority of ticlopidine in the reduction of strokes was seen in both males and females. Save for a reversible severe neutropenia in 0.86% of patients on ticlopidine, ticlopidine related side effects were relatively benign and reversible. The Canadian American Ticlopidine Study compared ticlopidine to placebo in patients with completed major strokes. The cumulative event rates for the primary outcome of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately following randomization consistent with a constant risk reduction of about 30% in the ticlopidine group. The data of the Canadian American Ticlopidine Study provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke. Ticlopidine reduced the risk of vascular events by 30%. In conclusion, sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone to stroke prevention. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit-risk ratio a reasonable one.