CONTEXT: The efficacy and safety of metformin for obesity in children and adolescents remains unclear. OBJECTIVE: To assess the efficacy and safety of metformin via systematic review. DATA SOURCES: Data sources included PubMed, Embase, the Cochrane Library, Scopus, and ClincalTrials.gov (inception to November 2019). STUDY SELECTION: We selected randomized controlled trials (RCTs) in which researchers assessed the efficacy and safety of metformin with lifestyle interventions, compared with a placebo with lifestyle interventions, in children and adolescents with obesity. DATA EXTRACTION: Two researchers independently extracted data and assessed quality. The primary outcomes were mean changes from baseline in BMI, BMI z score, homeostatic model assessment of insulin resistance, and gastrointestinal adverse effects. RESULTS: Twenty-four RCTs (1623 patients; range: 16 to 151) were included. Ages ranged from 4 to 19 years, and follow-up ranged from 2 months to 2 years. Metformin resulted in a modest decrease in BMI (range of mean values: −2.70 to 1.30 vs −1.12 to 1.90), BMI z score (range of mean values: −0.37 to −0.03 vs −0.22 to 0.15), and homeostatic model assessment of insulin resistance (range of mean values: −3.74 to 1.00 vs −1.40 to 2.66). Metformin resulted in a higher frequency of gastrointestinal adverse effects (range: 2% to 74% vs 0% to 42%). LIMITATIONS: The available evidence is of varying quality, with high heterogeneity between trials, suggesting some uncertainty in the benefits of metformin in this population. CONCLUSIONS: With this systematic review of RCTs, we suggest that metformin has modest but favorable effects on weight and insulin resistance and a tolerable safety profile among children and adolescents with obesity.