BACKGROUND: Some observational studies have not confirmed the beneficial effects of antihypertensive drug treatment on the incidence of stroke and coronary heart disease as demonstrated in randomized controlled clinical trials (RCTs). This contradiction is probably due to the biased comparison in most observational studies between treated hypertensive patients and prognostically different reference groups such as normotensives or untreated hypertensives regardless of their severity of hypertension and coexistence of other cardiovascular risk factors. OBJECTIVE: To assess the effect of the pharmacologic treatment of hypertension under everyday circumstances on the incidence of stroke. METHODS: Approximately 45 000 men and women aged >20 years were examined in 2 population-based studies in the Netherlands. A cohort of 2616 hypertensive subjects who were either pharmacologically treated for hypertension (n=1318) or untreated hypertensives who were “candidates” for pharmacologic treatment on the basis of the severity of their hypertension and the presence of other cardiovascular risk factors (n=983) was followed up for a mean duration of 4.6 years and follow-up was complete for 2369 (91%) subjects. RESULTS: In this observational study, compared to untreated hypertensive subjects who were “candidates” for pharmacologic treatment, subjects who were pharmacologically treated for hypertension had, after adjustment for differences in prognostic factors, a 39% [95% confidence interval (CI): 3-61%] reduced risk of stroke. About 46 [95%CI: 29-599] hypertensive patients need to be treated pharmacologically for 5 years to prevent one stroke in the general Dutch population. CONCLUSION: When a prognostically comparable reference group is used, the pharmacological treatment of hypertension under everyday circumstances appears to be effective in the reduction of the incidence of stroke. The relative risk reduction that we found was similar to those published on the basis of results from RCTs.