BACKGROUND: The present study was designed to investigate whether the prior use of aspirin could influence the severity of the manifestation of acute coronary artery syndromes, given the well-documented observations that aspirin can prevent myocardial infarction, stroke, and death in cardiovascular disease. METHODS AND RESULTS: A series of 539 consecutive patients admitted to the Coronary Care Unit of a General Hospital was carefully characterized in a study with an ambidirectional design, with regard to previous medical history, aspirin use, and subsequent hospital diagnosis. Among the 214 patients previously taking aspirin, the hospital diagnosis was myocardial infarction in 24% and unstable angina in 76% compared with 54% and 46%, respectively, among the 325 not taking aspirin (P < .0001), for a reduction in the odds ratio of myocardial infarction with aspirin of 72% (95% CI, 59% to 90%). The decrease in odds was homogeneous in all subsets studied and independent of age, sex, previous angina, or previous myocardial infarction. The myocardial infarction was of a Q-wave type in 62% of aspirin users compared with 76% of nonusers (P < .05). By multivariate analysis, previous aspirin use was a strong predictor of unstable angina versus myocardial infarction and the only independent predictor of non-Q-wave versus Q-wave myocardial infarction. CONCLUSIONS: This study, thus, suggests a shift to less severe manifestation of acute coronary syndromes with aspirin use, implying that the failure of the drug in many patients with an acute coronary syndrome is only partial and that aspirin has the potential of attenuating the severity of the underlying acute thrombotic disease process.