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. To determine whether noninvasive ventilation improves the outcome of weaning from invasive mechanical ventilation. Multicenter, randomized trial. Three respiratory intensive care units. Intubated patients with chronic obstructive pulmonary disease and acute hypercapnic respiratory failure. 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. Arterial blood gases, duration of mechanical ventilation, time in the intensive care unit, occurrence of nosocomial pneumonia, and survival at 60 days. 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. 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.