OBJECTIVE Heated and humidified high flow nasal cannula oxygen therapy (HFNC) represents a new alternative to conventional oxygen therapy that has not been evaluated in the emergency department (ED). We aimed to study its feasibility and efficacy in patients exhibiting acute respiratory failure presenting to the ED. METHODS Prospective, observational study in a university hospital's ED. Patients with acute respiratory failure requiring > 9 L/min oxygen or with ongoing clinical signs of respiratory distress despite oxygen therapy were included. The device of oxygen administration was then switched from non-rebreathing mask to HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning HFNC. Feasibility was assessed through caregivers' acceptance of the device in terms of practicality and perceived effect on the subjects, evaluated by questionnaire. RESULTS Seventeen subjects, median age 64 y (46-84.7 y), were studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC was associated with a significant decrease in both dyspnea scores: Borg scale from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1-5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min) to 25 breaths/min (21-28 breaths/min) (P < .001), and S(pO(2)) increased from 90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated and no adverse event was noted. Altogether, 76% of healthcare givers declared preferring HFNC, as compared to conventional oxygen therapy. CONCLUSIONS HFNC is possible in the ED, and it alleviated dyspnea and improved respiratory parameters in subjects with acute hypoxemic respiratory failure.