Background: Mechanical ventilation may contribute to lung injury and then enhance systemic inflammation. Optimal ventilatory parameters such as tidal volume (VT) and positive end expiratory pressure (PEEP) can be determined using different methods. Low flow pressure volume (P/V-LF) curve is a useful tool to assess the respiratory system mechanics and set ventilatory parameters. Aim: To set VT and PEEP according P/V-LF curve analysis and evaluate its effects on gas exchange and hemodynamic parameters. Materials and methods: Twenty seven patients underwent P/V-LF within the first 72 hours of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). P/V-LF curves were obtained from the ventilator and both lower and upper inflexion points determined. Gas exchange and hemodynamic parameters were measured before and after modifying ventilator settings guided by P/V-LF curves. Results: Ventilatory parameters set according P/V-LF curve, led to a rise of PEEP and reduction of VT: 11.6 ±2.8 to 14.1±2.1 cm H 2O, and 9.7±2.4 to 8.8±2.2 mL/kg (p<0.01). Arterial to inspired oxygen fraction ratio increased from 158.0±66 to 188.5±68.5 (p <0.01), and oxygenation index was reduced, 13.7±8.2 to 12.3±7.2 (p <0.05). Cardiac output and oxygen delivery index (IDO2) were not modified. Demographic data, gas exchange improvement and respiratory system mechanics showed no significant difference between patients with extra-pulmonary and pulmonary ALI/ARDS. There was no evidence of significant adverse events related with this technique. Conclusion: P/V-LF curves information allowed us to adjust ventilatory parameters and optimize gas exchange without detrimental effects on oxygen delivery in mechanically ventilated ALI/ARDS patients.