BACKGROUND: There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. METHODS: We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were amp;gt;40 years of age, were free from previous cancer, and had amp;gt;= 80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. RESULTS: During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. CONCLUSIONS: In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a amp;gt;30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.