Thirty-one patients with severe respiratory failure who were failing volume controlled conventional ratio ventilation were placed on pressure controlled inverse ratio ventilation (PC-IRV) for a total of 4,426 patient-hours. The PC-IRV resulted in a reduction of minute ventilation from 22 +/- 1.0 L/min (mean +/- SEM) to 15 +/- 0.7 L/min. Peak inspiratory pressure (PIP) was reduced from 66 +/- 2.3 cm H2O to 46 +/- 1.6 cm H2O and positive end expiratory pressures (PEEP) from 15 +/- 1.0 cm H2O to 2.5 +/- 0.5 cm H2O. Mean airway pressure increased from 30 +/- 1.7 cm H2O to 35 +/- 1.7 cm H2O. Oxygenation (PaO2) improved from 69 +/- 4.0 mm Hg to 80 +/- 4.5 mm Hg. The PaCO2 and arterial pH were not significantly changed. There were no significant changes in mean hemodynamic pressures. A lung compromise index (FIO2.PIP.10/PaO2) retrospectively distinguished between successful and unsuccessful PC-IRV episodes. These data suggest that PC-IRV can be successfully and safely implemented in critically ill patients with severe respiratory failure over prolonged periods of time resulting in significant improvement in oxygenation at lower minute volume, peak airway pressure and PEEP requirements.