Direct His‐bundle pacing (DHBP) produces rapid sequential multisite synchronous ventricular activation and, therefore, would be an ideal alternative to right ventricular apical (RVA) pacing. In 54 patients with cardiomyopathy, ejection fraction (EF) 0.23 ± 0.11, persistent atrial fibrillation, and normal QRS < 120 ms. DHBP was attempted. This was successful in 39 patients. In seven patients, the effect of increasing heart rate on contractility (Treppe effect) was investigated. Twelve patients who also received a RVA lead underwent cardiopulmonary testing. After a mean follow‐up of 42 months, 29 patients are still alive with EF improving from 0.23 ± 0.11 to 0.33 ± 0.15. Functional class improved from 3.5 to 2.2. DP/dt increased at each pacing site (P < 0.05) as the heart rate increased to 60, 100, and 120 beats/min. Rise in dP/dt by DHBP pacing at 120 beats/min was at least 170 ± mmHg/s, greater than any other site in the ventricle (P < 0.05). Cardiopulmonary testing revealed longer exercise time (RVA 255 ± 110 s) (His 280 ± 104 s) (P < 0.05), higher O2 uptake (RVA 15 ± 4 mL/kg per minute) (His 16 ± 4 mL/kg minute) (P < 0.05), and later anaerobic threshold (RVA 126 ± 71 s) (His 145 ± 74 s) (P < 0.05) with DHBP compared to RVA pacing. Long‐term DHBP is safe and effective in humans. DHBP is associated with a superior Treppe effect and increased cardiopulmonary reserve when compared to RVA pacing. (PACE 2004; 27[Pt. II]:862–870)