Objective: To assess comparative benefits and harms across three airway management approaches (bag valve mask [BVM], supraglottic airway [SGA], and endotracheal intubation [ETI]) used by prehospital emergency medical services (EMS) to treat patients with trauma, cardiac arrest, or medical emergencies, and how they differ based on techniques and devices, EMS personnel and patient characteristics. Data sources: We searched electronic citation databases (Ovid® MEDLINE®, CINAHL®, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus®) from 1990 to September 2020. Review methods: We followed Agency for Healthcare Research and Quality Effective Health Care Program Methods guidance. Outcomes included mortality, neurological function, return of spontaneous circulation (ROSC), and successful advanced airway insertion. Meta-analyses using profile-likelihood random effects models were conducted, with analyses stratified by study design, emergency type, and age. Results: We included 99 studies involving 630,397 patients. We found few differences in primary outcomes across airway management approaches. For survival, there was no difference for BVM versus ETI or SGA in adult and pediatric patients with cardiac arrest or trauma. For neurological function, there was no difference for BVM versus ETI and SGA versus ETI in pediatric patients with cardiac arrest. There was no difference in BVM versus ETI in adults with cardiac arrest, but improved neurological function with BVM or ETI versus SGA. There was no difference in ROSC for patients with cardiac arrest for BVM versus ETI or SGA in adults and pediatrics, or SGA versus ETI in pediatrics. There was higher frequency of ROSC in adults with SGA versus ETI. For successful advanced airway insertion, there was higher first-pass success with SGA versus ETI for all patients except adult medical patients (no difference), and no difference in overall success using SGA versus ETI in adults. Conclusions: The currently available evidence does not indicate benefits of more invasive airway approaches based on survival, neurological function, ROSC, or successful airway insertion. Strength of evidence was low or moderate; most included studies were observational. This supports the need for high-quality randomized controlled trials to advance clinical practice and EMS education and policy, and improve patient-centered outcomes.