Objectives To examine the association between social media (SM) use and health-risk behaviours: alcohol/drug/tobacco/electronic nicotine delivery system (ENDS) use, unhealthy dietary behaviour, inadequate physical activity, gambling, anti-social, sexual risk, and multiple risk behaviours in adolescents aged 10-19 years. Design Systematic review and meta-analysis. Data sources Embase, MEDLINE, APA PsycINFO, SocINDEX, CINAHL, SSRN, SocArXic, PsyArXiv, MedRxiv, and Google Scholar (01/1997-06/2022). Methods Included studies reported a SM exposure (time spent, frequency of use, exposure to health-risk behaviour content or other SM activities) and ≥1 relevant outcome. Screening and risk of bias (RoB) assessments were completed independently by two reviewers. Synthesis without meta-analysis (SWiM) based on effect direction and random-effects meta-analyses were used. Effect modification was explored using meta-regression and stratification. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Results Of 17,077 studies screened, 126 were included (76 meta-analysed). The final sample included 1,431,534 adolescents (mean age:15.0 years). SWiM indicated harmful associations between SM and all health-risk behaviours in most included studies, except inadequate physical activity where beneficial associations were reported in 63.6% of studies. Frequent (vs infrequent) SM use was associated with increased alcohol consumption (OR 1.48, 1.32 to 1.62; n=383,670), drug use (1.28, 1.05 to 1.56; n=117,646), tobacco use (1.78, 1.45 to 2.19; n=424,326), sexual risk (1.78, 1.49 to 2.13; n=47,325), anti-social behaviour (1.73, 1.44 to 2.06; n=54,993), multiple risk behaviours (1.75, 1.30 to 2.35; n=43,571), and gambling (2.84, 2.04 to 3.97; n=26,537). Exposure to health-risk behaviour content on SM (vs no exposure) was associated with increased odds of ENDS use (1.73, 1.34 to 2.23; n=721,322), unhealthy dietary behaviour (2.12, 1.87 to 2.39; n=9424), and alcohol consumption (2.43, 1.25 to 4.71; n=14,731). For alcohol consumption, stronger associations were identified for exposure to user-generated content (3.21, 2.37 to 4.33) vs marketer-generated content (2.18, 0.96 to 4.97). For time spent on SM, use for ≥2hrs/day (vs <2hrs) increased odds of alcohol consumption (2.13, 1.56 to 2.92; n=12,390). GRADE certainty was moderate for unhealthy dietary behaviour, low for alcohol use and very low for other investigated outcomes. Conclusions Social media use is associated with adverse adolescent health-risk behaviours, but further high quality research is needed to establish causality, understand effects on health inequalities, and determine which aspects of social media are most harmful. Given the pervasiveness of social media, efforts to understand and reduce the potential risks adolescents face may be warranted. Funding, competing interests, data sharing Funded by the Medical Research Council, Chief Scientist Office, NHS Research Scotland and the Wellcome Trust. All authors declare no competing interests. Template data forms, data extracted, and data analysed are available from the corresponding author on request. Systematic review registration PROSPERO: CRD42020179766.