Objective To compare the effect of prone position ventilation (PPV) and supine position ventilation (SPV) on respiratory parameters, hemodynamics and chest CT imaging in patients with acute respiratory distress syndrome (ARDS). Methods 90 patients with ARDS were randomly divided into PPV group (n=45) and SPV group (n=45). They were given mechanical ventilation at different positions. The blood gas indexes [pH, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide(PaCO2) and oxygenation index (PaO2/FiO2)] and hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP)] were detected before mechanical ventilation, after 1h and 2h of mechanical ventilation. CT examination was performed before mechanical ventilation and after 48h of mechanical ventilation. The average CT value (CT mean) of the whole lung was analyzed quantitatively. Results PaO2 and PaO2/FiO2 in the two groups increased after mechanical ventilation(P<0.05). The PaO2 and PaO2/FiO2 in PPV group after 1h and 2h of mechanical ventilation were significantly higher than those in SPV group (P<0.05). There was no significant difference in PaO2 or PaO2/FiO2 between the two groups at different time points (P>0.05). There was no significant difference in HR or MAP between the two groups before and after mechanical ventilation (P>0.05). The CT mean in the two groups decreased significantly after mechanical ventilation, and it of PPV group was significantly smaller than that of SPV group(P<0.05). Conclusion PPV can significantly improve the arterial oxygenation and lung CT value in patients with ARDS, without obvious effect on hemodynamics.