To investigate the influence of hypertension on morbidity and mortality during rate and rhythm control in patients with persistent atrial fibrillation (AF). In the RAte Control vs. Electrical cardioversion (RACE) study, 522 patients (256 with hypertension) were randomized to rate or rhythm control. The occurrence of cardiovascular morbidity and mortality was compared between patients with and without hypertension. Patients with hypertension were older (69 +/- 8 vs. 67 +/- 9 years, P = 0.01), more female (P < 0.001), had more diabetes (P = 0.005), a higher CHADS(2) score (2.2 +/- 1.0 vs. 1.0 +/- 0.9, P < 0.001), and higher systolic and diastolic blood pressures. Septal and posterior wall thicknesses were higher in hypertensives. Complaints related to AF were similar. After a median follow-up of 2.4 (range 0-3.4) years more endpoints occurred in hypertensives (25 vs. 15%). Randomized treatment strategy, i.e. rate or rhythm control, influenced the occurrence of the primary endpoint only in hypertensives. Hypertensives treated with rhythm control experienced most endpoints (incidence rates/100 person-years 13.3 vs. 7.2, relative risk 0.5 [0.3-0.9], P = 0.02), mainly thromboembolic complications, adverse effects of antiarrhythmics, and pacemaker implantations. In persistent AF patients with hypertension, a pharmacological rhythm control approach is associated with enhanced cardiovascular morbidity and mortality. Therefore, rate-control strategy should be considered in these patients.