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Peri-intubation major adverse events (MAEs) are potentially preventable and associated with poor patient outcomes. Critically ill patients intubated in Emergency Departments, Intensive Care Units or medical wards are at particularly high risk for MAEs. Understanding the prevalence and risk factors for MAEs can help physicians anticipate and prepare for the physiologically difficult airway. We searched PubMed, Scopus, and Embase for prospective and retrospective observational studies and randomized control trials (RCTs) reporting peri-intubation MAEs in intubations occurring outside the operating room (OR) or post-anesthesia care unit (PACU). Our primary outcome was any peri-intubation MAE, defined as any hypoxia, hypotension/cardiovascular collapse, or cardiac arrest. Esophageal intubation and failure to achieve first-pass success were not considered MAEs. Secondary outcomes were prevalence of hypoxia, cardiac arrest, and cardiovascular collapse. We performed random-effects meta-analysis to identify the prevalence of each outcome and moderator analyses and meta-regressions to identify risk factors. We assessed studies' quality using the Cochrane Risk of Bias 2 tool and the Newcastle-Ottawa Scale. We included 44 articles and 34,357 intubations. Peri-intubation MAEs were identified in 30.5% of intubations (95% CI 25–37%). MAEs were more common in the intensive care unit (ICU; 41%, 95% CI 33–49%) than the Emergency Department (ED; 17%, 95% CI 12–24%). Intubation for hemodynamic instability was associated with higher rates of MAEs, while intubation for airway protection was associated with lower rates of MAEs. Fifteen percent (15%, 95% CI 11.5–19%) of intubations were complicated by hypoxia, 2% (95% CI 1–3.5%) by cardiac arrest, and 18% (95% CI 13–23%) by cardiovascular collapse. Almost one in three patients intubated outside the OR and PACU experience a peri-intubation MAE. Patients intubated in the ICU and those with pre-existing hemodynamic compromise are at highest risk. Resuscitation should be considered an integral part of all intubations, particularly in high-risk patients. [ABSTRACT FROM AUTHOR]