Pressure control ventilation (PCV), high frequency oscillation (HFO), and intratracheal pulmonary ventilation (ITPV) maybe used to provide lung protective ventilation in ARDS but the optimal approach remains controversial. Saline lavage was used to produce ARDS in 21 sheep randomly assigned to received PCV, HFO, and ITPV applied as follows: PEEP (PCV, ITPV) and mean airway pressure (HFO) were set in a pressure decreasing manner following lung recruitment that achieved a PaO2/FIO2 > 400 mmHg. Respiratory rates were 30/min, 120/min and 8 Hz respectively for PCV, ITPV, and HFO. Eucapnia was targeted with peak carinal pressure < 35 cmH2O. Animals were then ventilated for 4 hours. There were no differences among groups in gas exchange, hemodynamics or inflammatory mediators. VT (8.9 + or- 2.1 mL/kg PCV, 2.7 + or- 0.8 mL/kg ITPV, about 2.0 mL/kg HFO) and peak carinal pressure (30.6 + 2.6 cmH2O PCV, 22.3 + 4.8 cmH2O ITPV, about 24.3 cmH2O HFO) were higher in PCV ( P < 0.05). Histologic examination revealed greater lung injury in PCV than HFO or HTPV. PEEP and mean airway pressure set by a decreasing pressure trial following lung recruitment was less than Pflex.