Given controversies surrounding the net benefit of aspirin for primary prevention of cardiovascular disease (CVD) and recent evidence of its protective role against cancer, Seshasai et al present the largest literature-based meta-analysis to date on the wider effects of aspirin in this population. Using information from up to 9 relevant randomized controlled trials involving over 100 000 participants, the authors demonstrate that aspirin, given for a mean period of approximately 6 years, significantly reduced the risk of all CVD events (by 10%, with a number needed to treat of 120), although this was largely driven by reductions in risk of nonfatal myocardial infarction (20%; number needed to treat, 162). However, these benefits were importantly offset by an excess risk (30%) of clinically nontrivial bleeding events (number needed to harm, 73). Furthermore, there was no significant reduction in CVD death or all-cause mortality and, contrary to recent suggestions, there was no significant benefit of aspirin prophylaxis on cancer mortality. The authors conclude that routine use of aspirin for primary prevention of CVD is not warranted in contemporary practice, and any indications for its use are best considered on a case-by-case basis.