Low-dose aspirin (acetylsalicylic acid [ASA]; 75 to 100 mg/d) is widely used in the prevention of cardiovascular (CV) events based on the results of large-scale studies supporting a benefit. However, questions remain regarding the benefit-risk relationship in certain settings since long-term use of ASA is not devoid of risk. Incontrovertible evidence supports the benefits of ASA treatment, which exceed the risks, in patients who have had a previous CV event (myocardial infarction, stroke, unstable angina, or transient ischemic attack). Nonetheless, the question remains for those patients who have not had a previous event (primary prevention), where the risk of CV events is lower and, consequently, the absolute benefit is also lower than in patients who have a history of a CV event or its equivalent (secondary prevention). Recent evidence from large-scale clinical trials shows that administration of low-dose ASA is associated with a reduced risk of CV events with a corresponding small absolute increase in the risk of major bleeding (eg, gastrointestinal bleeding and hemorrhagic stroke). Although the benefit and the risk of low-dose ASA in primary prevention are numerically similar, the clinical consequences of an increased risk of bleeding and a decreased risk of a CV event may not be equivalent. If these data are applied to patients with higher levels of CV outcome risk, more patients may potentially benefit from aspirin use in primary prevention.