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Background: Anxiety and depressive disorders are prevalent in adolescents and young adults. However, most young people with mental health problems do not receive treatment. Computerized cognitive behavior therapy (cCBT) may provide an accessible alternative to face-to-face treatment, but the evidence base in young people is limited.Objective: The objective was to perform an up-to-date comprehensive systematic review and meta-analysis of the effectiveness of cCBT in treating anxiety and depression in adolescents and young adults compared with active treatment and passive controls. We aimed to examine posttreatment and follow-up effects and explore the moderators of treatment effects.Methods: We conducted systematic searches in the following six electronic databases: PubMed, EMBASE, PsycINFO, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials. We included randomized controlled trials comparing cCBT with any control group in adolescents or young adults (age 12-25 years) with anxiety or depressive symptoms. The quality of included studies was assessed using the Cochrane risk-of-bias tool for randomized trials, version 2.0. Overall quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Posttreatment means and SDs were compared between intervention and control groups, and pooled effect sizes (Hedges g) were calculated. Random-effects meta-analyses were conducted using Comprehensive Meta-Analysis software. Subgroup analyses and meta-regression analyses were conducted to explore whether age, guidance level, and adherence rate were associated with treatment outcome.Results: The search identified 7670 papers, of which 24 studies met the inclusion criteria. Most included studies (22/24) had a high risk of bias owing to self-report measures and/or inappropriate handling of missing data. Compared with passive controls, cCBT yielded small to medium posttreatment pooled effect sizes regarding depressive symptoms (g=0.51, 95% CI 0.30-0.72, number needed to treat [NNT]=3.55) and anxiety symptoms (g=0.44, 95% CI 0.23-0.65, NNT=4.10). cCBT yielded effects similar to those of active treatment controls regarding anxiety symptoms (g=0.04, 95% CI -0.23 to 0.31). For depressive symptoms, the nonsignificant pooled effect size favored active treatment controls (g=-0.70, 95% CI -1.51 to 0.11, P=.09), but heterogeneity was very high (I2=90.63%). No moderators of treatment effects were identified. At long-term follow-up, cCBT yielded a small pooled effect size regarding depressive symptoms compared with passive controls (g=0.27, 95% CI 0.09-0.45, NNT=6.58). No other follow-up effects were found; however, power was limited owing to the small number of studies.Conclusions: cCBT is beneficial for reducing posttreatment anxiety and depressive symptoms in adolescents and young adults compared with passive controls. Compared with active treatment controls, cCBT yielded similar effects regarding anxiety symptoms. Regarding depressive symptoms, however, the results remain unclear. More high-quality research involving active controls and long-term follow-up assessments is needed in this population.Trial Registration: PROSPERO CRD42019119725; https://tinyurl.com/y5acfgd9. [ABSTRACT FROM AUTHOR]