Substance use has detrimental short-term and long-term consequences for young people. Positive youth development (PYD) interventions, which favour promotion of positive assets over traditional risk reduction, have received attention recently as a possible intervention to prevent adolescent substance use. We aimed to synthesise the evidence on PYD interventions for reduction in substance use in young people.We searched 21 databases, including MEDLINE, PsycINFO, CINAHL and CENTRAL, and hand-searched key journals and websites. We included studies with more than half of participants aged 11-18 years where interventions meeting a pre-specified definition of PYD were delivered in community settings outside of normal school hours and did not target parents or young people with pre-defined conditions. Two reviewers screened records, assessed full-text studies for inclusion, and extracted data. A modified Cochrane risk of bias tool was used for quality assessment.Ten studies reported in 13 reports were included in our synthesis. PYD interventions did not have an effect of statistical or public health significance on any substance use, illicit drug use or alcohol outcomes in young people.Interventions were diverse in content and delivery. Our review suggests that existing PYD interventions subject to evaluation do not appear to have produced reductions in substance use of public health significance. However, these interventions may not be the best exemplars of a PYD approach. Therefore, our findings should not be taken as evidence for the ineffectiveness of PYD as a theory of change for reducing substance use among young people. Additional rigorous evaluation of PYD interventions is key before further investment. Evaluations were of highly variable quality. Though searches were extensive, we were unable to test for publication bias.