OBJECTIVE: Our meta-analysis aimed to evaluate the safety of procedural sedation and analgesia in pediatric emergency department (ED) settings by investigating the incidence of cardiac, respiratory, gastrointestinal, and neurological adverse events associated with different sedation medications. METHODS: In accordance with PRISMA guidelines, a comprehensive database search for randomized controlled trials was performed across ten databases from January 2005 to June 2024. Our inclusion criteria included randomized controlled trials involving children under 18 years old undergoing pediatric sedation and analgesia in the ED. Data on medication types, dosages, administration routes, and adverse events were extracted and analyzed. Primary endpoints included cardiac, respiratory, gastrointestinal, and neurological adverse events. RESULTS: Seventeen studies met the inclusion criteria, a total of 2,302 procedural sedations. The most common adverse events were vomiting, agitation, and hypoxia, which occurred in 104.9 [95% CI = 76.9-132.9], 37.5 [95% CI = 20.6-54.4], 38.3 [95% CI = 23.9-52.6] of each 1000 sedations, respectively. Other adverse events included apnea, hypotension, and the need for bag-valve mask ventilation, which occurred in 8.6 [95% CI: 3.5-13.6], 9.3 [95% CI: -1.4 to 20.1], and 13.5 [95% CI: 3.2-23.8] of each 1,000 sedations, respectively. Severe adverse events were rare, with no reported instances of intubation and only one case of laryngospasm. Subgroup analyses revealed varying incidence rates of adverse events across different sedation protocols, with ketamine and its combinations showing higher rates of specific respiratory complications. CONCLUSIONS: Procedural sedation in pediatric EDs is generally safe, with a low incidence of adverse events, such as vomiting, agitation, and hypoxia. Life-threatening respiratory adverse events are extremely rare. Our findings thus support the careful selection and monitoring of sedation protocols to minimize risks.