In a meta-analysis published in June 2003, we reported that new and old classes of antihypertensive drugs had similar long-term efficacy and safety. Furthermore, we observed that in clinical trials in hypertensive or high-risk patients gradients in systolic blood pressure (SBP) accounted for most differences in outcome. To test whether our previous conclusions would hold, we updated our quantitative overview with new information from clinical trials published before 2005. To compare new and old antihypertensive drugs, we computed pooled odds ratios from stratified 2 x 2 contingency tables. In a meta-regression analysis, we correlated these odds ratios with corresponding between-group differences in SBP. We then contrasted observed odds ratios with those predicted from gradients in SBP. The main finding of our overview was that reduction in SBP largely explained cardiovascular outcomes in the recently published actively controlled trials in hypertensive patients and in placebo-controlled secondary prevention trials. The published results suggested that dihydropyridine calcium-channel blockers might offer a selective benefit in the prevention of stroke and inhibitors of the renin-angiotensin system in the prevention of heart failure. For prevention of myocardial infarction, the published results were more equivocal, because of the benefit of amlodipine over placebo or valsartan in 2 trials, whereas other placebo-controlled trials of calcium-channel blockers or angiotensin converting enzyme inhibitors did not substantiate the expected benefit with regard to cardiac outcomes. In conclusion, the hypothesis that new antihypertensive drugs might influence cardiovascular prognosis over and beyond their antihypertensive effect remains unproven. Our overview emphasizes the need of tight blood pressure control, but does not allow determining to what extent blood pressure must be lowered for optimal cardiovascular prevention.