In 1988, the Physicians' Health Study (PHS) demonstrated a conclusive 44% reduction in risk of a first myocardial infarction, while the much smaller British Doctors' Trial showed no significant effect. Since this time, 3 subsequent trials of aspirin in primary prevention of vascular diseases have been published. A meta-analysis of these 5 trials showed that among 55 580 randomized participants (11 466 women), there was a statistically significant reduction in risk of a first nonfatal myocardial infarction of 32% due to aspirin use (relative risk, 0.68; 95% confidence interval, 0.59-0.79). The evidence provides strong support for the initial findings from the landmark PHS that aspirin use reduces risk of a first myocardial infarction in apparently healthy individuals. For individuals in whom the risk of a first vascular event is 10% or more over 10 years, the benefits of aspirin use are likely to outweigh the risks.