OBJECTIVES: To assess what proportion of patients treated with low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular events discontinue this treatment, and to identify risk factors for discontinuation. METHODS: The Health Improvement Network UK primary care database was used to identify individuals aged 50–84 years with ≥2 prescriptions of low-dose ASA (75–300mg/day) in 2000–2007 (n=35,639). The study cohort was followed from the first day after the initial prescription until the earliest occurrence of one of the following: ASA discontinuation (a period of ≥90 days after the last prescription would have been used up [assuming full compliance], with no refill of the prescription during this time); death; diagnosis of an alcohol-related condition or cancer; or the end of the study period. The mean follow-up time was 2.5 years. RESULTS: Almost one-third of patients discontinued low-dose ASA (n=11,729; incidence: 13.1 per 100 person-years; 95% confidence interval [CI]: 12.9–13.4). The incidence of discontinuation was higher in the first year of follow-up (26.7 per 100 person-years; 95% CI: 26.1–27.3) than the rest of the study period (6.8 per 100 person-years; 95% CI: 6.6–7.0). The risk of discontinuation was 42–67% higher in patients with an initial indication of unstable angina, ischaemic heart disease or cerebrovascular disease than those with an initial indication of myocardial infarction. Current use of proton pump inhibitors (PPIs) was associated with a significant reduction in the risk of discontinuation (odds ratio [OR]: 0.92; 95% CI: 0.87–0.98; compared with no PPI use). Individuals taking PPIs from the same time as their ASA treatment were at particularly low risk of ASA discontinuation (OR: 0.74; 95% CI: 0.69–0.79). CONCLUSIONS: Discontinuation of low-dose ASA treatment is common, especially in the first year of treatment. Concomitant PPI use reduces the risk of ASA discontinuation.