Objective: To evaluate whether drug treatment for mild-to-moderate hypertension in middle-aged patients improves survival and to study how the conflicting results of individual trials may be explained. Study selection: A meta-analysis was performed, including seven randomized trials in mild-to-moderate hypertensive (diastolic blood pressure 90–114 mmHg) middle-aged patients. Data extraction: A comparison was made between all-cause mortality and fatal coronary heart disease and stroke in the intervention and control group of the individual trials, using a method of meta-analysis based on weighted linear regression. Results: In trials with a high all-cause mortality rate (>6 per 1000 patient-years) in the control group, antihypertensive drug treatment increased life expectancy. When all-cause mortality in the control group was low, treatment showed no effect or even an opposite effect. Findings on mortality from coronary heart disease were similar, whereas drug treatment decreased stroke mortality irrespective of the incidence of stroke in the control group. Conclusions: Drug treatment for mild-to-moderate hypertension in middle-aged patients may reduce all-cause mortality and the risk of fatal coronary events when treatment is initiated in those beyond a certain baseline mortality risk. Drug treatment in hypertensive patients at a lower mortality risk has no influence on or may even increase mortality.