Prolonged duration of endotracheal mechanical ventilation (ETMV) is associated with an increased morbidity and mortality in intensive care unit (ICU) patients. The aim of this study was to assess the usefulness of noninvasive ventilation (NIV) as a systematic extubation and weaning technique to reduce the duration of ETMV in acute-on-chronic respiratory failure (ACRF). Among 53 consecutively intubated patients admitted for ACRF, we conducted a prospective, randomized controlled trial of weaning in 33 patients who failed a 2-h T-piece weaning trial (2 h-WT) although they met simple criteria for weaning. Conventional invasive pressure support ventilation (IPSV) was used as the control weaning technique in 16 patients (IPSV group), and NIV was applied immediately after extubation in 17 patients (NIV group). The two weaning groups were similar for type of chronic respiratory failure (CRF), pulmonary function data, age, Simplified Acute Physiology Score (SAPS II), and severity of ACRF on admission. The characteristics of the two groups were also similar at randomization. In the IPSV group, 12 of 16 patients (75%) were successfully weaned and extubated, versus 13 of 17 (76.5%) in the NIV group (p = NS). NIV like IPSV significantly and similarly improved gas exchange in relation to that achieved during 2 h-WT (p < 0.05). The duration of ETMV was significantly shorter in the NIV (4.56 +/- 1.85 d) than in the IPSV group (7.69 +/- 3.79 d) (p = 0. 004). NIV also reduced the mean period of daily ventilatory support, but increased the total duration of ventilatory support related to weaning (3.46 +/- 1.42 d, versus 11.54 +/- 5.24 d with NIV; p = 0. 0001). Most patients in the IPSV group developed complications related to ETMV and/or the weaning process, but the difference was not significant (nine of 16 versus six of 17). The durations of ICU and hospital stays and the 3-mo survival were similar in the two groups. In conclusion, NIV permits earlier removal of the endotracheal tube than with conventional IPSV, and reduces the duration of daily ventilatory support without increasing the risk of weaning failures. NIV should be considered as a new and useful systematic approach to weaning in patients with ACRF who are difficult to wean.