To assess the cardiorespiratory effects of a prolonged application of inverse ratio ventilation (IRV), we compared IRV (I/E = 2) with conventional ventilation (CV) (I/E = 0.5), applied for 6 h each in a randomized order, with constant tidal volume (VT) and total positive end-expiratory pressure (PEEP(tot)) in eight patients with acute respiratory distress syndrome (ARDS). After 1 h, IRV resulted in a lower peak inspiratory pressure (PIP) (28.2 +/- 1.5 versus 35.6 +/- 1.7 cm H2O, p < 0.05), an unchanged plateau pressure, and a higher mean airway pressure (MAP) (17.8 +/- 0.8 versus 15.6 +/- 0.5 cm H2O, p < 0.05) than CV. No significant difference in Pa(O2) and shunt fraction (QS/QT) was observed (83 +/- 7 mm Hg and 40 +/- 4% in CV versus 92 +/- 14 mm Hg and 35 +/- 3% in IRV, respectively). The Pa(CO2) was lower in IRV (48 +/- 3 versus 55 +/- 5 mm Hg, p < 0.05). Cardiac index (CI) and oxygen delivery (D(O2)) were lower in IRV (3.7 +/- 0.4 L/min/m2 and 500 +/- 61 ml/min/m2 versus 4.6 +/- 0.5 L/min/m2 and 617 +/- 80 ml/min/m2, respectively, p = 0.05 for both). Regardless of the considered parameter, no significant difference was observed between results after 1, 2, 4, and 6 h in each mode. We conclude that IRV at a ratio that results in a significant intrinsic PEEP does not improve Pa(O2), enhances CO2 elimination, decreases cardiac output (CO), and does not exert any time-dependent effect.