Lung protective ventilation strategies are recommended in acute respiratory distress syndrome to avoid ventilator associated lung injury, a recently characterized complication of mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is an unconventional ventilation strategy which may achieve this goal. We reviewed our experience with HFOV in six severely burned patients with acute respiratory distress syndrome. The mean age (+/- SD) of the patients was 34 +/- 13 years, and the mean TBSA burn was 52 +/- 10%, with a mean full-thickness injury of 49 +/- 12%. HFOV was initiated as "rescue therapy" in three patients with oxygenation failure (mean PaO2/FIO2 ratio of 71 +/- 8 and mean oxygenation index [OI] of 42 +/- 3) that was unresponsive to conventional ventilation (mean FIO2, 1.0 +/- 0; mean positive end expiratory pressure, 14.8 +/- 2.8 cm H2O; and mean inhaled nitric oxide, 20 +/- 0 ppm). In the other three cases, HFOV was initiated "prophylactically" as a lung protective ventilation strategy in an attempt to prevent further respiratory deterioration. All six patients showed a rapid and substantial improvement in oxygenation after initiation of HFOV, with significant improvements in the PaO2/FIO2 and OI by 12 hours (P = 0.02). In four patients HFOV was also used during anesthesia and surgery, where a total of 10 procedures involving a mean excision and closure of 15 +/- 7% TBSA burns was performed. Five of the six patients died, but none died because of oxygenation failure. In three patients death resulted from sepsis and multiple organ dysfunction syndrome; their mean PaO2/FIO2 was 107 +/- 31 and their mean OI was 30 +/- 11 immediately before death. Two patients with multiple organ dysfunction syndrome died after withdrawal of life support; their mean PaO2/FIO2 and OI were 178 +/- 31 and 18 +/- 2 respectively, at the time of this decision. Although HFOV had no impact on mortality, it played a useful role in the supportive management of burn patients with severe oxygenation failure unresponsive to conventional ventilation. Importantly, HFOV allowed surgery to proceed in patients who may have otherwise been too unstable to go to the operating room. As far as we are aware, this is the first report of the use of intraoperative HFOV in burn patients.