OBJECTIVE: Low adherence to antihypertensive drug (AHT) treatment may limit patient's benefits in terms of a reduction of cardiovascular and cerebrovascular disease. This study investigated the relationship between persistence with antihypertensive drugs and risk of myocardial infarction (MI) or stroke in daily practice. METHODS: From the PHARMO record linkage system comprising, among other medical information, the medication histories and hospital discharge diagnoses of >2 million inhabitants in The Netherlands, new users of AHT were identified between 1993-2002. Persistence with AHT was determined by summing the number of days of continuous treatment (gaps between dispensings <60 days). Persistent patients remained on AHT for 24 months. The outcome of interest was the first hospital admission for MI or stroke occurring two or more years after initiation of AHT therapy. Patients were classified at high, intermediate or low cardiovascular risk based on other cardiovascular drug use and hospitalizations during the first two years of follow-up. RESULTS: The study included 98,485 patients of whom 16% were at high cardiovascular risk. About 50% (n=48,548) of all patients were persistent with AHT for two years. Multivariate analyses showed that persistent users of AHT had a statistically significant lower risk for MI/stroke compared to non-persistent users (RRadj=0.88; 95%CI: 0.82-0.94). The association was stronger in the low/intermediate risk group (RRadj=0.85; 95%CI: 0.79-0.92) than in the high risk group (RRadj=0.95; 95%CI: 0.83-1.09). CONCLUSION: Non-persistent use of AHT in daily practice leads to increased risk of hospitalizations for MI or stroke.