OBJECTIVE: Animal models suggest that high-frequency ventilation with low tidal volumes and high positive end-expiratory pressure (PEEP) minimize secondary injury to the lung. We hypothesized that using a high-frequency pressure-control mode of ventilation with high PEEP in children with severe acute respiratory distress syndrome (ARDS) would be associated with improved survival. DESIGN: The study was a retrospective and prospective clinical study at a 24-bed tertiary care pediatric critical care unit. Fifty-three patients with severe ARDS were studied during a 37-month period, 30 prospectively and 23 retrospectively. Severe ARDS was defined as (1) rapid onset of severe bilateral infiltrates of noncardiac origin, (2) partial pressure of oxygen (arterial)/fraction of inspired oxygen less than 200 on PEEP of 6 cm H₂O or more for 24 hours or longer, and (3) Murray disease severity score greater than 2.5. All patients meeting these criteria underwent ventilation in the pressure-control mode; the protocol for ventilation had the following general guidelines: (1) fraction of inspired oxygen limited to 0.5, (2) mean airway pressure titrated with PEEP to maintain arterial partial pressure of oxygen at 55 mm Hg or greater (7.3 kPa), (3) peak inspiratory pressure minimized to allow hypercapnia (arterial partial pressure of carbon dioxide, 45 to 60 mm Hg [6.0 to 8.0 kPa]), and (4) ventilator rates of 40 to 120/min. Percutaneous thoracostomy and mediastinal tubes were placed for treatment of air leak. RESULTS: The survival rate was 89% (47/53) in children with severe ARDS. Nonsurvivors had significantly higher peak inspiratory pressures (75 vs 40 cm H₂O, p = 0.0006), PEEP (23 vs 17 cm H₂O, p = 0.0004), mean airway pressure (40 vs 28 cm H₂O, p = 0.04), alveolar-arterial oxygen gradient (579 vs 540 mm Hg, p = 0.03), and oxygenation index (43 vs 19, p = 0.0008) than survivors. Air leak was present in 51% of patients; there was no difference in the incidence of air leak between survivors and nonsurvivors (p = 0.42). CONCLUSIONS: The high-frequency positive-pressure mode of ventilation was safe and was associated with an improved survival rate (89%) for children with severe ARDS. Limitation of both inspired oxygen and tidal volume, along with aggressive treatment of air leak, may have contributed to the improved survival rate. (J PEDIATR 1996;129:566-73)