BACKGROUND: In a quantitative overview of published trials, we investigated whether some pharmacological properties of antihypertensive drugs, besides reduction in blood pressure, explain cardiovascular outcomes in hypertensive or high-risk patients. METHODS: Across trials, using meta-regression, we correlated odds ratios with differences in systolic blood pressure between study groups. We then compared odds ratios of benefit observed in recent trials with those predicted by metaregression on the basis of the differences in systolic pressure between randomised groups. RESULTS: Significant differences in systolic pressure between randomised groups (experimental minus reference) were observed in the ALLHAT (-2/+1), CAPPP(-3/-1) and NORDIL (-3.1/+0.2) trials. Furthermore, the differences in achieved systolic and/or diastolic pressure between study groups were also significant in the hypertension trials which involved untreated control patients, as well as in MIDAS (-3.5/ approximately 0 mm Hg), HOPE (-3.3/-1.0 mm Hg), PART2 (-5/-4 mm Hg), and SCAT (4/-2 mm Hg) (1). The differences between the observed odds ratios and those predicted by the meta-regression between outcome and difference in systolic pressure did not reach statistical significance except for the NORDIL trial, in which the risk of stroke was lower on diltiazem than on the older drugs despite a 3.1 mm Hg higher systolic pressure on the calcium-channel blocker. CONCLUSIONS: The finding that in the reviewed trials blood pressure reduction largely accounted for outcome emphasizes the desirability of blood pressure control. The hypothesis that converting-enzyme inhibitors or alpha-blockers might influence cardiovascular prognosis over and beyond their antihypertensive effect remains unproved.