This study was conducted to evaluate the effectiveness and safety of a practical protocol for titrating positive end-expiratory pressure (PEEP) involving recruitment maneuver (RM) and decremental PEEP. Seventeen consecutive patients with acute lung injury who underwent PEEP titration were included in the analysis. After baseline ventilation, RM (continuous positive airway pressure, 35 cm H2O for 45 sec) was performed and PEEP was increased to 20 cmH2O or the highest PEEP guaranteeing the minimal tidal volume of 5 mL/kg. Then PEEP was decreased every 20 min in 2 cmH2O decrements. The "optimal" PEEP was defined as the lowest PEEP attainable without causing a significant drop (>10%) in PaO2. The "optimal PEEP" was 14.5 ± 3.8 cmH2O. PaO2 /FI O2 ratio was 154.8 ± 63.3 mmHg at baseline and improved to 290.0 ± 96.4 mmHg at highest PEEP and 302.7 ± 94.2 mmHg at "optimal PEEP", both significantly higher than baseline (p<0.05). Static compliance was significantly higher at "optimal" PEEP (27.2 ± 10.4 mL/ cmH2O) compared to highest PEEP (22.3 ± 7.7 mL/cmH2O) (p<0.05). Three patients experienced transient hypotension and one patient experienced atrial premature contractions. No patient had gross barotrauma. PEEP titration protocol involving RM and PEEP decrement was effective in improving oxygenation and was generally welltolerated.