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Objectives: To compare clinical impact after early initiation of high-flow nasal cannula oxygen therapy (HFNC) versus standard oxygen in patients admitted to an emergency department (ED) for acute hypoxemic respiratory failure., Methods: We performed a prospective before-after study at EDs in two centers including patients with acute hypoxemic respiratory failure defined by a respiratory rate above 25 breaths/min or signs of increased breathing effort under additional oxygen for a pulse oximetry above 92%. Patients with cardiogenic pulmonary edema or exacerbation of chronic lung disease were excluded. All patients were treated with standard oxygen during the first period and with HFNC during the second. The primary outcome was the proportion of patients with improved respiratory failure 1 h after treatment initiation (respiratory rate ≤ 25 breaths/min without signs of increased breathing effort). Dyspnea and blood gases were also assessed., Results: Among the 102 patients included, 48 were treated with standard oxygen and 54 with HFNC. One hour after treatment initiation, patients with HFNC were much more likely to recover from respiratory failure than those treated with standard oxygen: 61% (33 of 54 patients) versus 15% (7 of 48 patients), P < 0.001. They also showed greater improvement in oxygenation (increase in PaO 2 was 31 mm Hg [0-67] vs. 9 [-9-36], P = 0.02), and in feeling of breathlessness., Conclusions: As compared to standard oxygen, patients with acute hypoxemic respiratory failure treated with HFNC at the ED had better oxygenation, less breathlessness and were more likely to show improved respiratory failure 1 h after initiation., (Copyright © 2019 Elsevier Inc. All rights reserved.)