BACKGROUND AND OBJECTIVE: Although prone positioning has been reported to improve gas exchange, prone positioning alone does not seem to be sufficient to increase systemic oxygen transport in an acute lung injury. The objective of this study was to investigate whether the combined therapy of low dose nitric oxide (NO) inhalation and prone positioning has an additive effect on the oxygenation and hemodynamics in patients with severe ARDS. PATIENTS AND METHODS: Twelve patients with ARDS were included. Prone positioning alone, later combined with nitric oxide inhalation (5~10 ppm) from the supine position (baseline) were performed with serial measurement of gas exchange, respiratory mechanics and hemodynamic at sequential time points. The patient was regarded as a responder to prone positioning if an increase in PaO2/FiO2 of more than 20 mmHg at 30 min or 120 min intervals after prone positioning was observed compared to that of the baseline. The same criterion was applied during nitric oxide inhalation. RESULTS: Eight patients (66.5%) responded to prone positioning and ten patients (83.3%) including the eight just mentioned responded to the addition of NO inhalation. The AaDO2 level also decreased promptly with the combination of prone positioning and NO inhalation compared to that of prone positioning alone (191+/-109 mmHg. 256137 mmHg, P<0.05). Hemodynamic parameters and lung compliance did not change significantly during prone positioning only. Following the addition of NO inhalation to prone positioning, the mean pulmonary artery pressure and pulmonary artery occlusion pressure decreased and cardiac output, stroke volume and oxygen delivery increased (P0.05) compared to those of prone 120 min. CONCLUSION: These findings indicate that NO inhalation would provide additional improvement in oxygenation and oxygen transport to mechanically ventilated patients with ARDS who are in a prone position.