PurposeInformation regarding the use of aspirin for patients with no known cardiovascular disease remains conflicting. We performed an updated meta-analysis to evaluate the efficacy and safety of aspirin for primary prevention of cardiovascular disease.Patients and methodsPubMed, MEDLINE, and Cochrane library databases were searched for randomized controlled trials comparing aspirin with placebos or no treatment published up until November 1, 2018. The primary efficacy endpoint was all-cause death. The secondary endpoints included cardiovascular death, myocardial infarction, and stroke. The safety endpoints included major bleeding, gastrointestinal bleeding, and hemorrhagic stroke.ResultsFourteen studies were included. Aspirin use was associated with a lower risk of myocardial infarction than placebo use or no treatment (risk ratio [RR], 0.83, 95% confidence interval [CI]: 0.73–0.95, P = 0.005). Additionally, compared with the control groups, aspirin use was not associated with a lower risk of all-cause mortality or cardiovascular mortality. In terms of safety, aspirin use was associated with a higher risk of major bleeding (RR, 1.40, 95% CI: 1.25–1.57, P = 0.000), gastrointestinal bleeding (RR, 1.58, 95% CI: 1.25–1.99, P = 0.000), and hemorrhagic stroke (RR, 1.30, 95% CI: 1.06–1.60, P = 0.011). Furthermore, the treatment effect was not significantly modified by patients’ clinical characteristics. No publication bias was present.ConclusionAspirin use reduced the myocardial infarction risk in patients without known cardiovascular disease, but had no effect in terms of reducing the risk of all-cause death, cardiovascular death, and stroke, and increased the risk of major bleeding, gastrointestinal bleeding, and hemorrhagic stroke.