Importance Nonoperative management (NOM) has emerged as a potential alternative to surgery for acute uncomplicated appendicitis in children; however, while short-term outcomes are often favorable, concerns remain about treatment durability, complication rates, and long-term failure. An updated meta-analysis of randomized clinical trials (RCTs) may help clarify the comparative safety and effectiveness of NOM vs appendectomy. Objective To evaluate the safety and effectiveness of NOM compared with appendectomy for uncomplicated appendicitis in children using the highest level of available evidence. Data Sources A systematic review of PubMed, Embase, Scopus, Cochrane, and Web of Science was conducted from inception through March 2025 to identify randomized clinical trials comparing NOM with surgical management in pediatric patients. Study Selection RCTs comparing NOM vs surgical management in pediatric patients younger than 18 years were included. Nonrandomized and quasi-randomized studies were excluded. Data Extraction and Synthesis Data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses were conducted using random-effects models. Risk of bias was assessed independently by multiple reviewers. Trial sequential analysis was performed to determine whether the evidence was sufficiently robust and conclusive. Main Outcomes and Measures The primary outcomes were treatment failure and treatment success in 1 year and major complications (Clavien-Dindo grade ≥IIIb). Secondary outcomes included time to return to school and time to return to normal activity. Results Of 1246 studies screened, 7 RCTs, including 1480 pediatric patients, met inclusion criteria. Treatment failure was significantly higher in the NOM group than in the appendectomy group at 1 year (risk ratio [RR], 4.97; 95% CI, 3.57-6.91; I 2 = 0.0%). Treatment success was significantly lower in the NOM group at 1 year (RR, 0.67; 95% CI, 0.60-0.75; I 2 = 31.1%). Major complications classified as Clavien-Dindo grade IIIb or worse were more frequent in the NOM group (RR, 33.37; 95% CI, 7.89-141.05; I 2 = 9.5%). Appendicitis recurred at a rate of 18.47 events/100 observations (95% CI, 12.62-25.07 events/100 observations; I 2 = 48.5%) among patients who received NOM. NOM, compared with appendectomy, was associated with a modestly faster return to school (mean difference, –1.36 days; 95% CI, −2.64 to −0.08 days; P = .04; I 2 = 57.7%) and return to normal activities (–4.93 days; 95% CI, −8.68 to −1.19 days; P = .01; I 2 = 87.2%), although this may be offset by subsequent readmissions or reintervention. Trial sequential analysis demonstrated the robustness and conclusiveness of primary outcomes. Conclusions and Relevance In contrast to earlier studies, this meta-analysis found significantly higher treatment failure and major complication rates within a year with NOM among children and adolescents. The meta-analysis provides pediatricians and pediatric surgeons with up-to-date data to inform shared decision-making with families and encourage individualized, patient-centered treatment.