DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or postextubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital length of stay, 30-day hospital readmissions, hospital-acquired pneumonia, days of intubation or reintubation, intensive care unit (ICU) admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adult patients with acute respiratory failure treated in a hospital setting (including emergency departments, hospital wards, intermediate or step-down units, and ICUs). RECOMMENDATION 1A: ACP suggests that clinicians use high-flow nasal oxygen rather than noninvasive ventilation in hospitalized adults for the management of acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use high-flow nasal oxygen rather than conventional oxygen therapy for hospitalized adults with postextubation acute hypoxemic respiratory failure (conditional recommendation; low-certainty evidence).