OBJECTIVE: To determine whether the use of non-potassium-sparing diuretics and beta-blockers is associated with an excess risk for sudden cardiac death in hypertensive patients. DESIGN: Case-control study. SETTING: Rotterdam, the Netherlands. PATIENTS: 257 case-patients who had died suddenly while receiving drug therapy for hypertension and 257 living controls also receiving drug therapy for hypertension. MEASUREMENTS: Detailed information on medication use and clinical characteristics of all case-patients and controls was collected from the files of general practitioners. Additional information on medication use was obtained from computerized pharmacy records. RESULTS: Patients receiving non-potassium-sparing diuretics had an increased risk for sudden cardiac death (relative risk, 1.8 [95% CI, 1.0 to 3.1]) compared with a reference group treated primarily with potassium-sparing diuretics. The corresponding relative risk for beta-blocker use was 1.7 (CI, 1.1 to 2.6). The use of non-potassium-sparing diuretics without beta-blockers was associated with a higher risk for sudden death (relative risk, 2.2 [CI, 1.1 to 4.6]) than was concomitant use of non-potassium-sparing diuretics and beta-blockers (relative risk, 1.4 [CI, 0.6 to 3.0]). The risk for sudden cardiac death among recipients of non-potassium-sparing diuretics was more pronounced in those who had been receiving the diuretic for less than 1 year and in those aged 75 years or younger. CONCLUSIONS: The use of non-potassium-sparing diuretics and beta-blockers is associated with an increased risk for sudden cardiac death. This association may offset part of the mortality benefit of these drugs in the treatment of hypertension.