BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary disease, mechanical ventilation is often needed. The rate of weaning failure is high in these patients, and prolonged mechanical ventilation increases intubation-associated complications. OBJECTIVE: To determine whether noninvasive ventilation improves the outcome of weaning from invasive mechanical ventilation. DESIGN: Multicenter, randomized trial. SETTING: Three respiratory intensive care units. PATIENTS: Intubated patients with chronic obstructive pulmonary disease and acute hypercapnic respiratory failure. INTERVENTION: A T-piece weaning trial was attempted 48 hours after intubation. If this failed, two methods of weaning were compared: 1) extubation and application of noninvasive pressure support ventilation by face mask and 2) invasive pressure support ventilation by an endotracheal tube. MEASUREMENTS: Arterial blood gases, duration of mechanical ventilation, time in the intensive care unit, occurrence of nosocomial pneumonia, and survival at 60 days. RESULTS: At admission, all patients had severe hypercapnic respiratory failure (mean pH, 7.18+/-0.06; mean PaCO2, 94.2+/-24.2 mm Hg), sensory impairment, and similar clinical characteristics. At 60 days, 22 of 25 patients (88\%) who were ventilated noninvasively were successfully weaned compared with 17 of 25 patients (68\%) who were ventilated invasively. The mean duration of mechanical ventilation was 16.6+/-11.8 days for the invasive ventilation group and 10.2+/-6.8 days for the noninvasive ventilation group (P = 0.021). Among patients who received noninvasive ventilation, the probability of survival and weaning during ventilation was higher (P = 0.002) and time in the intensive care unit was shorter (15.1+/-5.4 days compared with 24.0+/-13.7 days for patients who received invasive ventilation; P = 0.005). Survival rates at 60 days differed (92\% for patients who received noninvasive ventilation and 72\% for patients who received invasive ventilation; P = 0.009). None of the patients weaned noninvasively developed nosocomial pneumonia, whereas 7 patients weaned invasively did. CONCLUSIONS: Noninvasive pressure support ventilation during weaning reduces weaning time, shortens the time in the intensive care unit, decreases the incidence of nosocomial pneumonia, and improves 60-day survival rates.