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Background: Humidified, high-flow nasal cannula (HFNC) enables mucociliary clearance, accurate oxygen measurement, precise control of flow, and low-level positive airway pressure. There is sparse information concerning the timing of HFNC on patient outcomes such as incidence of adverse events during hospitalization, ICU stay, and post-ICU stay., Methods: This is a retrospective analysis of a heterogeneous population of medical and trauma ICU patients who received HFNC therapy in a critical care setting. The study sample included 145 subjects who were admitted to the ICU and received HFNC therapy between March 2012 and February 2014. HFNC was delivered by the Fisher & Paykel Optiflow system., Results: Of the 145 subjects who received HFNC, 35 (24.1%) received mechanical ventilation before HFNC, 21 (14.5%) received mechanical ventilation after HFNC, and 89 (61.3%) never received mechanical ventilation. Delay to first HFNC was moderately associated with unplanned ICU admission and was strongly correlated with the development of ventilator-associated pneumonia. Subjects with a greater length of time between ICU admission and first use of HFNC experienced significantly longer stays in the ICU and post-ICU periods, even after controlling for adverse events and mechanical ventilation., Conclusions: Study results provide preliminary evidence that early use of HFNC is beneficial in a medical and trauma ICU population, as it was associated with decreased ICU and post-ICU lengths of stay and reduced incidence of adverse events. This suggests that HFNC should be considered early in the ICU as first-line oxygen therapy., (Copyright © 2015 by Daedalus Enterprises.)