Purpose <p>Perioperative respiratory adverse event (PRAE) is one of the most common complications in pediatric anesthesia. We aimed to evaluate the efficacy of perioperative pharmacological interventions to prevent the development of PRAE in children undergoing noncardiac surgery.</p> Methods <p>PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched for randomized controlled trials (RCT) of prophylactic pharmacological interventions for PRAE among surgical children from inception to 5 August 2024. Pairwise meta-analyses were conducted to compare the effects of an intervention with placebo or another intervention on overall PRAE and their subtypes, including laryngospasm, bronchospasm, oxygen desaturation, airway obstruction, coughing and stridor. Risk of bias was assessed using the Cochrane Collaboration tool.</p> Results <p>Seven categories of prophylactic interventions were identified. Twenty-nine RCTs with 4452 children were included. Compared with placebo, lidocaine reduced the odds ratio (OR) of overall PRAE ( 0.27 [95% CI] [0.17, 0.42]) and laryngospasm (0.38 [0.22, 0.67]); dexmedetomidine reduced the OR of PRAE (0.31 [0.12, 0.76]), laryngospasm (0.31 [0.10, 0.91]), coughing (0.24 [0.14, 0.41]) and oxygen desaturation (0.54 [0.35, 0.84]); β₂-adrenoreceptor agonists reduced the OR of PRAE (0.45 [0.24, 0.83]), coughing (0.36 [0.13, 0.95]) and oxygen desaturation (0.66 [0.45, 0.98]). Compared with sevoflurane induction, intravenous propofol induction lowered the OR of PRAE (0.35 [0.16, 0.74]), laryngospasm (0.17 [0.06, 0.48]) and airway obstruction (0.32 [0.17, 0.63]).</p> Conclusions <p>The meta-analysis demonstrated prophylactic potential of lidocaine, dexmedetomidine, β₂-adrenoreceptor agonists and propofol induction technique against PRAE, but it should be interpreted cautiously due to inconsistent PRAE definition and correlation of subtypes within the composite outcome.</p> Trial registration <p>PROSPERO (CRD42020220028). Registered 11 December 2020. Updated 3 September 2024.</p>