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Patients with acute cardiogenic pulmonary edema may develop respiratory failure. Noninvasive respiratory support should be initiated rapidly to avoid tracheal intubation. The aim of this study is to compare the efficacy of continuous positive airway pressure (CPAP) delivered by the Boussignac CPAP device and bilevel positive airway pressure (bilevel PAP) in patients with acute respiratory failure caused by acute cardiogenic pulmonary edema.This prospective multicenter randomized study was conducted in 3 emergency departments. Patients were assigned to Boussignac CPAP through a facemask or to bilevel PAP, in addition to standard therapy. The main outcome was a combined criterion (tracheal intubation, death, or acute myocardial infarction). Complications, durations of ventilation, and hospitalization were also assessed.After 1 hour of ventilation and at the end of the ventilation period, clinical parameters of respiratory distress and blood gas exchange significantly improved in each treatment arm. No significant differences were observed between the Boussignac CPAP and bilevel PAP arms for the combined criterion (5% versus 12%, respectively; odds ratio [OR] 0.4; 95% confidence interval [CI] 0.0 to 1.9) and also for severe complications (9% versus 6%; OR 1.5; 95% CI 0.3 to 9.9), duration of ventilation (median for both groups 2 hours; interquartile range [IQR] 1.2 to 3.0 hours), duration of hospitalization (CPAP 8.5 [IQR 6 to 14] days; bilevel PAP 10 [IQR 7 to 16] days), or intrahospital mortality (8% versus 14%; OR 1.8 [IQR 0.4 to 8.8]). Similar results were obtained among hypercapnic patients (PaCO2 >45 mm Hg). Whatever the ventilation support used, the combined criterion and severe complications were more frequently observed among hypercapnic patients.Both Boussignac CPAP and bilevel PAP appeared effective in rapidly improving respiratory distress even in hypercapnic patients, but they were not different in terms of patient outcome.