Aims This study aimed to use an umbrella review methodology to capture the range of outcomes that were associated with low-dose aspirin and to systematically assess the credibility of this evidence. Methods Aspirin is associated with several health outcomes, but the overall benefit/risk balance related to aspirin use is unclear. We searched three major databases up to 15 August 2019 for meta-analyses of observational studies and randomized controlled trials (RCTs) including low-dose aspirin compared to placebo or other treatments. Based on random-effects summary effect sizes, 95% prediction intervals, heterogeneity, small-study effects and excess significance, significant meta-analyses of observational studies were classified from convincing (class I) to weak (class IV). For meta-analyses of RCTs, outcomes with random effects P-value < .005 and a moderate/high GRADE assessment, were classified as strong evidence. From 6802 hits, 67 meta-analyses (156 outcomes) were eligible. Results Observational data showed highly suggestive evidence for aspirin use and increased risk of upper gastrointestinal bleeding (RR = 2.28, 95% CI: 1.97-2.64). In RCTs of low-dose aspirin, we observed strong evidence for lower risk of CVD in people without CVD (RR = 0.83; 95% CI: 0.79-0.87) and in general population (RR = 0.83; 95% CI: 0.79-0.89), higher risk of major gastrointestinal (RR = 1.47; 95% CI: 1.26-1.72) and intracranial bleeding (RR = 1.34; 95% CI: 1.18-1.53), and of major bleedings in people without CVD (RR = 1.62; 95% CI: 1.26-2.08). Conclusion Compared to other active medications, low-dose aspirin had strong evidence for lower risk of bleeding, but also lower comparative efficacy. Low-dose aspirin significantly lowers CVD risk and increases risk of bleeding. Evidence for multiple other health outcomes is limited.