We propose to conduct a randomized, double-blind, placebo-controlled trial in women testing low (300 mg/every other day) and very low (100 mg/every other day) doses of aspirin in the primary prevention of cardiovascular disease. The primary aim of the trial is to assess the effect of treatment with aspirin (either dose) compared to placebo on the combined endpoint of all important vascular events (nonfatal myocardial infarction, nonfatal stroke and total vascular mortality). Secondary aims of the trial are to evaluate the effect of treatment with aspirin (either dose) compared to placebo on the separate endpoints of total myocardial infarction, total stroke, and total vascular mortality and to compare the two doses of aspirin for side effects and efficacy. This trial will be conducted among 41,600 postmenopausal female US nurses, aged 50 years or older, with no previous history of cardiovascular disease. Letters of invitation and baseline questionnaires asking about past medical history, risk factors for cardiovascular disease and possible contraindications to aspirin will be sent to approximately 1.39 million potential participants. The nurses who are both willing and eligible to participate will be randomly assigned to either of the aspirin regimens and be sent calendar packs for a three-month run-in period. The run-in will exclude poor compliers and those unable to tolerate study medication prior to randomization and thus increase the power of the trial to detect small to moderate effects as well as allow for a reliable assessment of relative short term side effects of each aspirin dose. Participants who comply with the treatment regimen during the run-in period and who remain willing and eligible will be re-randomized to one of the three groups, low dose aspirin (300 mg every other day), very low dose aspirin (100 mg every other day), or placebo. To maintain high compliance, pills will be packaged in convenient, one-month calendar packs. Every six months, additional calendar packs and questionnaires asking about compliance, the occurrence of any side effects and the development of endpoints will be mailed. Endpoints will be confirmed by review of medical records by an endpoints committee of physicians. This trial will provide the only reliable data worldwide on these important and timely public health issues in women.