The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood-pressure-lowering regimens. We aimed to estimate effects of strategies based on different drug classes (angiotensin-converting-enzyme [ACE] inhibitors, calcium antagonists, angiotensin-receptor blockers [ARBs], and diuretics or beta blockers) or those targeting different blood pressure goals, on the risks of major cardiovascular events and death. We did seven sets of prospectively-designed overviews with data from 29 randomised trials (n=162341). The trial eligibility criteria, primary outcomes, and main hypotheses were specified before the result of any contributing trial was known. In placebo-controlled trials the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22%; 95% CI 17-27) or calcium antagonists (18%; 5-29). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15%; 5-24). ARB-based regimens reduced the risks of total major cardiovascular events (10%; 4-17) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or beta blockers, although ACE-inhibitor-based regimens reduced blood pressure less. There was evidence of some differences between active regimens in their effects on cause-specific outcomes. For every outcome other than heart failure, the difference between randomised groups in achieved blood pressure reduction was directly related to the observed difference in risk. Treatment with any commonly-used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.