We propose to conduct a five-year randomized, double-blind, placebo-controlled trial of the effect of alternate-day consumption of a ews.mg aspirin tablet primarily on cardiovascular mortality (but also on total mortality) among male U.S. physicians, 50 to 75 years of age. We mailed study materials to a random sample of 5000 subjects, and their replies indicated that we will enroll 21,900 apparently healthy men. Physicians who are eligible and willing to participate will be assigned at random to taking either a single 325 mg aspirin tablet or placebo every other day. Every six months participants will be sent new supplies in monthly calendar packs and follow-up questionnaires asking about their compliance and recent health. Deaths in all randomized subjects will be documented by death certificates. Under the null hypothesis we would expect about 500 cardiovascular deaths and over 1000 total deaths in each group during the 41/2 years of data collection. A Mantel-Haenszel pooled analysis of all trials completed to date, including AMIS, indicate a 20% reduction in reinfarction and a 9% reduction in total mortality. (Repeating this analysis using the AMIS values adjusted by the Cox procedure gives reductions of 24% in reinfarction and 13% in total mortality, both significant.) Thus, under reasonable alternative hypotheses (ie, a 20% reduction due to aspirin), this trial will have power greater than 90%. A subsidiary aim will be to assess the effect of ingestion of beta-carotene on the risk of developing cancer in this same population. To do this, we will randomly assign half of each aspirin/placebo treatment group to taking one 30 mg capsule of either beta-carotene of its placebo every other day. Our pilot study results and our consideration of possible interactions indicate that we can accomplish this important scientific objective without affecting the sensitivity (or the cost) of the aspirin component. The study will thus be a 2x2 factorial in which each participant takes a single tablet or capsule daily.