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ContextMore than 50 million US adults take aspirin regularly for long-term prevention of cardiovascular disease, typically either 81 mg/d or 325 mg/d. Controversy remains regarding the most appropriate long-term daily dose.ObjectiveTo review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy, and safety.Evidence AcquisitionA systematic review of the English-language literature was undertaken using MEDLINE and EMBASE (searched through February 2007) and the search term aspirin or acetylsalicylic acid and dose. The search was limited to clinical trials and was extended by a review of bibliographies of pertinent reports of original data and review articles. Published prospective studies using different aspirin dosages in the setting of cardiovascular disease were included.Evidence SynthesisAlthough pharmacodynamic data demonstrate that long-term …