Aspirin is the drug most commonly used to prevent thrombotic events and the dose ranges from 75 mg to 325 mg/day (www.fda.gov/ohrms/dockets/98fr//102398c.txt). A recent analysis has estimated that the admissions for adverse effects of drugs has shown that aspirin is one of the most common causal agents (BMJ 2004, 329:15-9). The bleeding of the mucosa of the gastrointestinal tract is the major source of bleeding related to aspirin, because of inhibition of gastroprotective prostacyclins (BMC Med 2006; 4:22). The aim of the authors is to establish the incidence and risk factors of adverse events of aspirin in trials in primary prevention. The authors performed a post hoc study on the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance; NEJM 2006, 354: 1706-17). The CHARISMA study was a multicenter study, double-blind, randomized, clopidogrel (75 mg/day) versus placebo in patients with age greater than or equal to 45 years, with established atherosclerotic disease or asymptomatic but at high risk, at all patients were also given a low-dose of aspirin (dose between 75 and 162 mg/day). The primary efficacy end point was considered the occurrence of myocardial infarction, stroke or death due to cardiovascular disease. The primary safety end point was considered the occurrence of severe bleeding. According to the daily dose of aspirin three groups have been identified: less than 100 mg/day (75 or 81 mg, n = 7180), 100 mg (n = 4961) and more than 100 mg (150 or 162 mg, n = 3454). The incidence of the primary end point by the end of follow up (average 28 months), did not differ by aspirin dose, the incidence of severe bleeding increased with increasing dose of aspirin. The conclusions of the analysis are the following: daily dose of aspirin greater than 100 mg is not associated with a clear benefit in patients taking aspirin alone or in patients taking clopidogrel, a daily dose of aspirin between 75 mg and 81 mg can optimize the efficacy and safety for patients requiring long-term prevention, especially for those taking dual antiplatelet therapy.