SummaryImportanceThe effectiveness of anti‐obesity medications for children and adolescents is unclear.ObjectiveTo update the evidence on the benefits and harms of anti‐obesity medication.Data SourcesCochrane CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP (1/1/16–17/3/23).Study SelectionRandomized controlled trials ≥6 months in people <19 years living with obesity.Data Extraction and SynthesisScreening, data extraction and quality assessment conducted in duplicate, independently.Main Outcomes and MeasuresBody mass index (BMI): 95th percentile BMI, adverse events and quality of life.ResultsThirty‐five trials (N = 4331), follow‐up: 6–24 months; age: 8.8–16.3 years; BMI: 26.2–41.7 kg/m². Moderate certainty evidence demonstrated a −1.71 (95% confidence interval [CI]: −2.27 to −1.14)‐unit BMI reduction, ranging from −0.8 to −5.9 units between individual drugs with semaglutide producing the largest reduction of −5.88 kg/m² (95% CI: −6.99 to −4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: −11.88 percentage points (95% CI: −18.43 to −5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I² = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance.Conclusions and RelevanceAnti‐obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event.