This clinical policy from the American College of Emergency Physicians addresses a key issue in the evaluation and management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. A writing subcommittee conducted a systematic review of the literature to derive evidence-based recommendations to answer the following clinical question: In emergency department patients diagnosed with acute carbon monoxide poisoning, does hyperbaric oxygen therapy compared with normobaric (room pressure) oxygen therapy improve long-term neurocognitive outcomes? Evidence was graded, and recommendations were made based on the strength of the available data.