Despite its universal use, the optimal dose of aspirin from an efficacy and safety perspective remains unclear. There are wide variations in international practice and a lack of consensus as to the most appropriate dose of aspirin in patients with acute coronary syndromes (ACS), mainly because of the wide range of doses evaluated in early randomized trials of aspirin versus placebo. Comparisons of aspirin dose have been based on observational studies or indirect comparisons from meta-analysis of antiplatelet trials. These studies have suggested that aspirin, in doses>or=300 mg, is similar to aspirin doses 75-100 mg/d for prevention of major vascular events, but that higher doses increase the risk of major bleeding complications. Recently, the CURRENT-OASIS study, a randomized head-to-head comparison of higher-dose (>or=300 mg/d) versus low-dose aspirin (75-81 mg/d) for 1 month in over 25,000 patients with ACS referred for an early invasive strategy demonstrated similar outcomes between higher- and low-dose aspirin for efficacy, with no difference in the risk of major bleeding complications. Results from this mega-trial suggest that low-dose or higher-dose aspirin is a reasonable option in ACS patients undergoing an early invasive strategy.