Objective: Early severe graft dysfunction, as manifested by hypoxia and pulmonary hypertension, occurs in 10% to 20% of lung transplant recipients. We retrospectively investigated whether inhaled nitric oxide would reduce human lung allograft dysfunction by comparing postoperative hemodynamic data, gas exchange, and outcome in lung transplant recipients with early graft dysfunction treated with or without nitric oxide. Method: Among 243 adult lung transplant procedures, there were 32 patients (13.2%) in whom immediate severe allograft dysfunction developed (arterial oxygen tension/inspired oxygen concentration ratio < 150). Group 1 (n = 17) included patients who underwent transplantation before nitric oxide became available in our center and were treated conventionally. Group 2 (n = 15) included those treated with nitric oxide as soon as severe allograft dysfunction was diagnosed. Duration of nitric oxide therapy (20 to 60 ppm) was 15 to 217 hours (average 84 hours). Results: In group 2, nitric oxide lowered mean pulmonary artery pressure from 30 ± 2 to 26 ± 2 mm Hg (p < 0.05), improved the ratio of arterial oxygen tension to inspired oxygen fraction from 88 ± 10 to 153 ± 30 (p < 0.05) within 1 hour, and caused a sustained improvement in these parameters during extended therapy. Mean arterial pressure and cardiac index were unchanged during nitric oxide therapy. Transient methemoglobinemia (>6%) developed in two patients. However, no complications were associated with nitric oxide use. Duration of mechanical ventilation was 17 ± 5 days in group 1 and 12 ± 3 days in group 2. Four patients had airway complications in group 1, whereas no airway complication was encountered in group 2. Mortality was 24% (4/17) in group 1 and 7% (1/15) in group 2. Conclusion: Nitric oxide improves oxygenation and decreases pulmonary artery pressure without systemic circulatory effects in patients with severe allograft dysfunction. Furthermore, in these patients, nitric oxide may shorten postoperative mechanical ventilation time and reduce airway complications and mortality.