This meta-analysis investigates whether antihypertensive drugs offer cardiovascular protection beyond blood pressure lowering in hypertensive or high-risk patients. Nine randomized trials involving 62,605 hypertensive patients were analyzed. Calcium-channel blockers and angiotensin-converting-enzyme (ACE) inhibitors provided similar overall cardiovascular protection compared to older drug classes like diuretics and β-blockers. Calcium-channel blockers showed a greater reduction in stroke risk (13.5%, 95% CI 1.3-24.2, p=0.03) but a lesser reduction in myocardial infarction risk (19.2%, 95% CI 3.5-37.3, p=0.01). Heterogeneity was significant due to high cardiovascular event risks in some trials. Meta-regression analysis across 27 trials (136,124 patients) confirmed that odds ratios for cardiovascular outcomes could be explained by differences in systolic pressure between groups. The findings emphasize the importance of blood pressure control, with all antihypertensive drugs showing similar long-term efficacy and safety. Calcium-channel blockers may be particularly effective in stroke prevention.This meta-analysis investigates whether antihypertensive drugs offer cardiovascular protection beyond blood pressure lowering in hypertensive or high-risk patients. Nine randomized trials involving 62,605 hypertensive patients were analyzed. Calcium-channel blockers and angiotensin-converting-enzyme (ACE) inhibitors provided similar overall cardiovascular protection compared to older drug classes like diuretics and β-blockers. Calcium-channel blockers showed a greater reduction in stroke risk (13.5%, 95% CI 1.3-24.2, p=0.03) but a lesser reduction in myocardial infarction risk (19.2%, 95% CI 3.5-37.3, p=0.01). Heterogeneity was significant due to high cardiovascular event risks in some trials. Meta-regression analysis across 27 trials (136,124 patients) confirmed that odds ratios for cardiovascular outcomes could be explained by differences in systolic pressure between groups. The findings emphasize the importance of blood pressure control, with all antihypertensive drugs showing similar long-term efficacy and safety. Calcium-channel blockers may be particularly effective in stroke prevention.