The objective of this study was to evaluate the efficacy of pressure control inverse ratio ventilation (PCIRV) in improving oxygenation in trauma patients with adult respiratory distress syndrome (ARDS) and to assess the potential risks associated with this form of treatment. This was a cohort study assessing the trends in hemodynamic and ventilatory parameters after the initiation of PCIRV, conducted at a community Level I trauma center intensive care unit. The study comprised 15 trauma patients developing severe, progressive ARDS [two or more of the following criteria: positive end-expiratory pressure (PEEP) >10 cm H2O; arterial partial pressure of oxygen divided by fraction of inspired oxygen (PaO2:FiO2) ratio <150; and peak inspiratory pressure (PIP) >45 cm H2O]: ten due to blunt chest injuries, three due to sepsis, and two due to fat emboli syndrome. PCIRV was initiated. Main outcome measures were PIP, PEEP (total, auto), oxygen saturation, cardiac index, oxygen delivery, PaO2:FiO2 ratio, compliance, evidence of complications of PCIRV, and mortality. Within 24 hours of conversion to PCIRV, the patients stabilized and the mean PaO2:FiO2 ratio rose from 96.3+/-57.8 to 146.8+/-91.1 (P<0.05) and PIP fell from 47.9+/-13.8 to 38.8+/-8.4 cm H2O; auto-PEEP increased from 0.5+/-1.9 to 7.5+/-5.6 cm H2O (P<0.05); oxygen delivery index remained stable (563+/-152 to 497+/-175 mL/min/m2); three patients developed evidence of barotrauma, one patient developed critical illness polyneuropathy, and two patients died (13%). PCIRV is an effective salvage mode of ventilation in patients with severe ARDS, but it is not without complications. Auto-PEEP levels and cardiac index should be monitored to ensure tissue oxygen delivery is maintained.