STUDY OBJECTIVE To assess whether pressure support ventilation (PSV) could be used as an alternative ventilatory mode to assist-control (A/C) ventilation in the treatment of respiratory failure. DESIGN A short-term (4-h) prospective study in which the beneficial effect of PSV on respiratory mechanics, gas exchange, arterial oxygenation, cardiovascular hemodynamics, and oxygen consumption was compared with A/C ventilation. SETTING ICU of a community hospital. PATIENTS Forty-five patients (mean age, 62.8 [11.8] years) with respiratory failure secondary to COPD, restrictive disorders, or neuromuscular disease requiring mechanical ventilatory support in the ICU were selected for study. INTERVENTIONS The mean duration of mechanical ventilation before the study was 7.16 (8.64) days. Patients were switched to the PSV mode of the mechanical ventilator for a period of 4 h after which conventional A/C ventilation was resumed. RESULTS Patients supported with PSV compared with A/C ventilation showed significantly higher tidal volume, minute ventilation, and inspiratory time in association with significantly lower pressure in the airway and I:E ratio. With regard to gas exchange data, an increase in dead space/tidal volume ratio (VD/VT), decrease in PaO2, and statistically but not clinically significant alteration of arterial oxygenation indexes were noted. However, when patients with COPD, restrictive disorders, and neuromuscular disease were compared, significant changes in arterial oxygenation parameters were found only in patients with restrictive disorders. There were significant decreases in heart rate, systolic pulmonary artery pressure, and pulmonary capillary wedge pressure when PSV was applied. Oxygen transport and oxygen consumption were unchanged. CONCLUSIONS PSV could be a possible alternative to A/C ventilation in patients with respiratory failure. PSV caused an increase in VD/VT in association with a significantly lower pressure in the airway and I:E ratio. Randomized studies are needed to define the long-term benefits of both respiratory modes and the conditions in which PSV may be a valuable alternative to A/C ventilation.