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Respiratory failure after extubation and reintubation is associated with increased morbidity and mortality.To assess the efficacy of noninvasive ventilation in averting respiratory failure after extubation in patients at increased risk.A prospective randomized controlled trial was conducted in 162 mechanically ventilated patients who tolerated a spontaneous breathing trial after recovery from the acute episode but had increased risk for respiratory failure after extubation. Patients were randomly allocated after extubation to receive noninvasive ventilation for 24 h (n = 79), or conventional management with oxygen therapy (control group, n = 83).The primary end-point variable was the decrease in respiratory failure after extubation. In the noninvasive ventilation group, respiratory failure after extubation was less frequent (13, 16 vs. 27, 33%; p = 0.029) and the intensive care unit mortality was lower (2, 3 versus 12, 14%; p = 0.015). However, 90-d survival did not change significantly between groups. Separate analyses of patients without and with hypercapnia (arterial CO2 tension greater than 45 mm Hg) during the spontaneous breathing trial showed that noninvasive ventilation improved intensive care unit mortality (0 vs. 4, 18%; p = 0.035) and 90-d survival (p = 0.006) in hypercapnic patients only; of them, 98% had chronic respiratory disorders.The early use of noninvasive ventilation averted respiratory failure after extubation and decreased intensive care unit mortality among patients at increased risk. The beneficial effect of noninvasive ventilation in improving survival of hypercapnic patients with chronic respiratory disorders warrants a new prospective clinical trial.