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Recruitment maneuvers (RMs) can expand collapsed alveoli in ventilated patients. The optimal method for delivering RMs is unknown. Purpose: To evaluate the safety and the respiratory and hemodynamic effects of a staircase recruitment maneuver (SRM) with decremental positive end expiratory pressure (PEEP) titration and the consequences of desaturation during the SRM in patients with early acute lung injury (ALI). Methods: In total, 20 consecutive patients with early ALI were enrolled and received an SRM. Patients were given 15 ± 3 cm H2O pressure-controlled ventilation. Positive end expiratory pressure was increased from baseline (range 10–18) to 20, 30, and 40 cm H2O every 2 minutes to achieve maximum alveolar pressure of 55 ± 3 cm H2O, then decreased at 3-minute intervals to 25, 22.5, 20, 17.5, and 15 cm H2O until a decrease of l% to 2% oxygen saturation from maximum was detected. Positive end expiratory pressure was left at the level where the fall in oxygen saturation occurred. Standard respiratory and circulatory variables, arterial and central venous gases were measured before, during, and after the SRM. Results: There were significant improvements in shunt fraction (36.3% ± 10% to 26.4% ± 14%, P < .001), oxygen saturation (93.4%± 2% to 96.8% ±3%, P = .007), partial pressure of oxygen, arterial (PaO2)/fraction of inspired oxygen ([FIO2]; 150±42 to 227±100, P = .004), lung compliance (33.9±9.1 to 40.1±11.4 mL/cm H2O, P < .01), and chest x-ray (CXR) after the SRM. Briefly, 80% of the patients responded and the response was maintained at 1 hour. In total, 8 patients desaturated 6.1% ±2.8% in SaO2 during the SRM but 5 of those improved SaO2 relative to baseline by the end of the SRM. Conclusions: In all, 80% of the patients with early ALI responded to the SRM with decremental PEEP titration. Desaturation during the SRM did not indicate a failed response 1 hour later.