BACKGROUND: The possibility that specific antihypertensive treatments may prevent the occurrence of stroke more effectively than other treatments remains unproved. We undertook a meta-analysis to assess whether calcium channel blockers (CCBs) are associated with a lesser risk of stroke as compared with other antihypertensive drugs. METHODS: Through Medline we identified 13 major studies conducted in hypertensive subjects for a total of 103,793 subjects. Overall, there were 4040 incident cases of stroke, 1789 among 43,053 subjects randomized to CCBs and 2251 among 60,740 subjects randomized to different antihypertensive drugs. RESULTS: Considering all 13 trials, a pooled reduction in the risk of stroke was observed among subjects allocated to CCBs (odds ratio 0.90, 95% confidence interval [95% CI] 0.84-0.96; P =.002). The risk of stroke was significantly lower among subjects allocated to dihydropyridine CCBs than among those randomized to alternative drugs (odds ratio 0.90, 95% CI 0.84-0.97; P =.006), whereas the effect of non-dihydropyridine CCBs did not achieve significance (odds ratio 0.92, 95% CI 0.81-1.04). In a meta-regression analysis of these trials, the protection from stroke conferred by CCBs appeared unrelated to the degree of systolic blood pressure reduction. CONCLUSIONS: These findings suggest that CCBs decrease the risk of stroke more effectively than other treatments in patients with essential hypertension and that such an effect might not be completely explained by a better antihypertensive response. Calcium channel blockers should be considered in hypertensive subjects at increased risk of stroke.