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In randomized studies of heterogeneous patients with hypoxemic acute respiratory failure, noninvasive positive pressure ventilation (NPPV) was associated with a significant reduction in endotracheal intubation. The role of NPPV in patients with acute respiratory distress syndrome (ARDS) is still unclear. The objective was to investigate the application of NPPV as a first-line intervention in patients with early ARDS, describing what happens in everyday clinical practice in centers having expertise with NPPV.Prospective, multiple-center cohort study.Three European intensive care units having expertise with NPPV.Between March 2002 and April 2004, 479 patients with ARDS were admitted to the intensive care units. Three hundred and thirty-two ARDS patients were already intubated, so 147 were eligible for the study.Application of NPPV.NPPV improved gas exchange and avoided intubation in 79 patients (54%). Avoidance of intubation was associated with less ventilator-associated pneumonia (2% vs. 20%; p < .001) and a lower intensive care unit mortality rate (6% vs. 53%; p < .001). Intubation was more likely in patients who were older (p = .02), had a higher Simplified Acute Physiology Score (SAPS) II (p < .001), or needed a higher level of positive end-expiratory pressure (p = .03) and pressure support ventilation (p = .02). Only SAPS II >34 and a Pao2/Fio2 ≤175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation.In expert centers, NPPV applied as first-line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.