The extent to which adolescents are influenced by their peers has been the focus of developmental psychological research for over 50 years. That research has yielded contradicting evidence and much debate. This study consists of a systematic review and meta-analysis, with the main aim of quantifying the effect of peer influence on adolescent substance use, as well as investigation into the factors that moderate this effect. Included studies needed to employ longitudinal designs, provide the necessary statistics to calculate cross-lagged regression coefficients controlling for target adolescent’s initial substance use, and comprise participants aged 10–19 years. A search of academic databases and reference lists generated 508 unique reports, which were screened using Covidence. The final inclusion criteria yielded a total of 99 effect sizes from 27 independent studies. A four-level meta-analytic approach with correction to allow the inclusion of multiple effect sizes from a given study was used to estimate an average effect size. Results revealed a significant effect of peer influence ($$\overline{\upbeta }$$
β
¯
= .147, p < .001), indicating that adolescents changed their substance use behaviour in accordance with their peers’ perceived or actual use. Moderation analyses found peer influence effects varied significantly as a function of substance use behaviour (categorised as alcohol, tobacco, marijuana, or composite substance use) and peer influence measure (perceived vs. actual peer report); however, no significant effects emerged in the multivariate moderation model simultaneously examining all five main moderators. These results suggest that adolescent substance use is affected by peer influence processes across multiple substance use behaviours and both directly and indirectly through perceived norms. This has significant implications for substance use prevention, including the potential of harnessing peer influence as a positive force and the need to target misperceptions of substance use.
