Aspirin is widely used for prevention of cardiovascular disease. In recent years randomized trials also suggested a preventive effect for various types of cancer. We aimed to assess, in a quantitative way, benefits and harms of aspirin for primary prevention of both cardiovascular disease and cancer for a general US population between 40 and 85 years of age.We used the Gail/National Cancer Institute approach for assessing benefits and harms. This approach provides a probability that a treatment is more beneficial than harmful and incorporates multiple outcomes, the importance of these outcomes, considers different outcome risks and treats mortality as a competing risk. Our main outcomes were the risks of seven types of cancer, myocardial infarction, ischemic and hemorrhagic stroke and gastrointestinal bleeding. We obtained effect estimates from recent meta-analyses of randomized trials and used baseline risks from the Centers for Disease Control. We conducted four sensitivity analyses to assess the influence of different assumptions about outcome risks and preferences and considered the sampling variation of the effect estimates for aspirin.The main analysis as well as the sensitivity analyses showed that aspirin has more benefits than harms. In the main analysis, the index (positive if number of prevented events > excess number of harm events over 10 years per 1,000 persons) ranged from 2 (95% CI 0.0 to 11.8; in women age 45 to 54 years) to 8 (95% CI -0.1 to 83.7; in men age 65 to 74 years). In the sensitivity analyses, the index was also positive for all age categories suggesting more benefits than harms.This study suggests an overall benefit of aspirin for primary prevention of cardiovascular disease and cancer based on population-based data. For individual preventive counseling, additional benefit harm analyses should explore which individuals should or should not take aspirin based on their risk profile for cardiovascular, cancer and gastrointestinal outcomes and based on their outcome preferences. Thereby, risk-stratified and preference-sensitive prevention could become a reality.