This clinical policy focuses on critical issues concerning the management of adult patients presenting to the emergency department (ED) with acute symptomatic carbon monoxide (CO) poisoning. The subcommittee reviewed the medical literature relevant to the questions posed. The critical questions are: Should hyperbaric oxygen (HBO2) therapy be used for the treatment of patients with acute CO poisoning; and Can clinical or laboratory criteria identify CO-poisoned patients who are most or least likely to benefit from this therapy. Recommendations are provided on the basis of the strength of evidence of the literature. Level A recommendations represent patient management principles that reflect a high degree of clinical certainty; Level B recommendations represent patient management principles that reflect moderate clinical certainty; and Level C recommendations represent other patient management strategies that are based on preliminary, inconclusive, or conflicting evidence, or based on committee consensus. This clinical policy is intended for physicians working in hospital-based EDs.