Background and Methods Patients undergoing orthotopic cardiac transplantation manifest reduced exercise capacity during the first postoperative year, which is related primarily to chronotropic incompetence of the denervated heart. To determine whether exercise capacity improves during the long term after transplantation, we prospectively studied 45 patients from 1 month to 6 years after cardiac transplantation by use of maximal treadmill exercise testing for measurement of exercise duration, peak heart rate, and peak Vo₂. All had normal left ventricular ejection fractions. Patients were categorized according to length of time since transplant and compared to 14 untrained normal subjects. Results Peak exercise heart rate and exercise duration were progressively higher as time after transplantation increased. However, patients who had undergone transplantation more than 2 years earlier continued to manifest a significant reduction in peak exercise heart rate (157 ± 3 beats/min vs 178 ± 14 beats/min) and reduced exercise duration (8.6 ± 0.5 minutes vs 13.2 ± 2.0 minutes) compared with controls. In contrast, peak Vo₂ was similar at all times after transplant and remained markedly reduced in patients who underwent transplantation more than 2 years earlier as compared with controls (22.1 ± 0.7 mL/kg/min vs 42.1 ± 9.1 mL/kg/min). The potential effects of 14 clinical variables on exercise performance were evaluated by regression modeling. Patients with poorly controlled hypertension had a shorter median exercise duration (7.4 minutes vs 9.7 minutes) and a lower median peak Vo₂ (20.3 mL/kg/min vs 23.2 mL/kg/min) compared with patients with normal or well-controlled blood pressure. Patients treated with calcium channel blockers for hypertension had greater chronotropic incompetence during exercise (peak heart rate 139 beats/min vs 158 beats/min). There was no relation between exercise capacity and recipient age, donor age, recipient sex, donor ischemic time, pretransplant diagnosis, length of peritransplant hospitalization, percentage of ideal body weight, left ventricular ejection fraction, frequency or severity of allograft rejection, or long-term use of oral prednisone therapy. Conclusions Exercise capacity, as measured by treadmill exercise time and peak heart rate, improves in the first 2 years after transplantation, but does not reach normal values in patients up to 6 years after transplant. Peak Vo₂ remains significantly reduced at all times after transplantation despite the presence of normal resting left ventricular systolic function. (Am Heart J 1998;136:465-73.)