Background: It has been reported that boys’ and girls’ physical activity (PA) levels decline throughout adolescence. Boys are at risk of physical inactivity during adolescence however, in intervention research they are an under-represented group relative to girls. It is suggested that the school environment may be central to developing interventions that support adolescents in meeting the current PA guidelines. The purpose of this systematic review and meta-analysis was to investigate the efficacy of school-based interventions to increase moderate to vigorous physical activity (MVPA) and muscle and bone strengthening exercise (MBSE) outcomes in adolescent males. Methods: This systematic review and meta-analysis followed the preferred reporting systems for meta-analyses guidelines and was registered on PROSPERO (Registration number: CRD42018091023). Eligible studies were published in English within peer-reviewed articles. Searches were conducted in three databases, with an additional grey literature search in Google Scholar. Studies with MVPA and MBSE as outcomes were included.Results: There were 51 data sets identified across 15 studies, from eight countries. Overall methodological quality of the studies was moderate to strong. Significant, small effect sizes were identified following a pooled analysis of all studies which aimed to increase MVPA and MBSE outcomes (g = 0.26, 95% CI = 0.15, 0.37, P = <.001). Interventions targeting MVPA were ineffective (g = -0.09, 95% CI -0.72, -0.53, P = 0.77). Interventions targeting MBSE evidenced a small to medium effect (g = 0.27, CI 0.16, 0.39, P = <.001). Sub-group analyses of MBSE delivery method resulted in small to medium effects: Upper limb MBSE (g = 0.23, 95% CI 0.03, 0.43, p = 0.02), lower limb MBSE (g = 0.21, 95% CI 0.09, 0.33, p <0.00), combined resistance activities (g = 0.22, 95% CI 0.05 – 0.39, p = <0.00), plyometric activities (g = 0.39, 95% CI 0.09, 0.68, p = 0.01), body weight (g = 0.21, 95% CI -0.00, 0.44, p = 0.05), and traditional MBSE methods (g = 0.43, 95% CI -0.09, 0.78, p = 0.01).Conclusions: School-based interventions which aim to increase MVPA in adolescent males were not effective. Interventions focused on MBSE demonstrated small to moderate effects. Traditional and plyometric methods of MBSE appear to be the most effective form of PA delivery in adolescent males. More quality research is required to assess the impact of MBSE delivered in the school environment in order to inform future intervention design.