To investigate the impact of exercise on adult allogeneic hematopoietic cell transplant recipients, we randomized 100 patients to either a structured walking regimen or to a control group with no formal exercise program. Starting on the day of admission for transplant, patients in the exercise arm were asked to walk on a treadmill twice a day for 15 minutes while in the hospital. After discharge, they were asked to walk once a day for 30 minutes. The effect of the exercise program was primarily measured by the change in the Karnofsky score (KPS) from transplant admission to day 100 posttransplant, which was scored by the attending physician who was blinded to the assigned exercise regimen. The decline in KPS was smaller in the exercise group than in the control group: 10 points versus 20 points. This difference was not statistically significant in the total study population (P = .21) but was statistically significant among the subset of older and less fit patients receiving nonmyeloablative pretransplant conditioning (P = .04). Sixty-four percent of patients on the exercise arm who had a baseline KPS <90 had a score ≥90 by day 100 compared to 18% of the control arm (P = .03). Thirty-two percent of patients with a baseline score ≥90 had a score ≥90 by day 100 in both groups (P = .99). Analyses of patients' self reported scores at the time of discharge for physical and emotional well-being showed that the exercise arm had better scores for physical well-being (P < .01). Among the subset of nonmyeloablative patients, scores for physical and emotional well-being were both higher in the exercise arm (P = .02). Length of hospitalization and survival were not different between the 2 study arms. We conclude that assignment of a structured walking regimen to patients can lead to better physical performance during the recovery period and by patient assessment, a better perceived physical and emotional state. In addition, exercise has a greater impact among patients who are less fit coming into transplant. Structured exercise may have a positive impact on physical and emotional recovery following transplant therapy and may accelerate patients' return to health and function.