Single-lung transplantation is an effective treatment for end-stage pulmonary failure caused by a variety of lung diseases. Although single-lung recipients may undergo a similar operative procedure, physiologic differences in the remaining native lung dictate differences in postoperative management and perhaps outcome. To examine these effects on the early results after single-lung transplantation, we retrospectively reviewed the course of 83 patients undergoing single-lung transplantation from September 1988 through July 1993. The cause of the lung disease was obstructive (OLD) in 43, idiopathic pulmonary fibrosis (IPF) in 16, and primary pulmonary hypertension (PPH) in 24 patients. The hospital mortality was 5% in OLD, 13% in IPF, and 8% in PPH. Gas exchange as demonstrated by alveolar-arterial oxygen gradients was worse after transplantation in patients with IPF (349 ± 159 mm Hg) or PPH (270 ± 171 mm Hg) compared with patients with OLD (174 ± 105 mm Hg; p < 0.05). Mean pulmonary artery pressures were higher in patients with IPF (28 ± 6 mm Hg) and PPH (26 ± 7 mm Hg) compared with patients with OLD (22 ± 5 mm Hg; p < 0.05). Peak airway pressures after transplantation were greater in patients with IPF (36 ± 6 cm H2O) compared with patients with OLD (28 ± 6 cm H2O; p < 0.01). Additionally, patients undergoing single-lung transplantation for IPF required more intensive hospital therapy as measured in intensive care unit days, ventilator time, and need for tracheostomy (12.5 ± 17.5 days, 12 ± 19.9 days, and 24%, respectively) compared with patients with OLD (3.1 ± 2.7 days, 2.3 ± 2.3 days, and 7%, respectively; p < 0.05) or PPH (7.8 ± 8.6 days, 7.7 ± 9.8 days, and 21%, respectively). These data emphasize the importance of the difference in the physiology between patients undergoing single-lung transplantation for obstructive, restrictive, and pulmonary vascular diseases with regard to optimal patient management and results.