Introduction: Few interventions have been successful in reducing the physical activity decline typically observed among adolescents. The aim of this paper is to report the 24-month effectiveness of a multicomponent school-based intervention (Physical Activity 4 Everyone) in reducing the decline in moderate to vigorous physical activity (MVPA) among secondary school students in disadvantaged areas of New South Wales, Australia. Study design: A cluster RCT was conducted in five intervention and five control schools with follow-up measures taken at 24 months post-randomization. Setting/participants: The trial was undertaken within secondary schools located in disadvantaged communities in New South Wales, Australia. Intervention: A multicomponent school-based intervention based on the Health Promoting Schools Framework was implemented. The intervention consisted of seven physical activity promotion strategies that targeted the curriculum (teaching strategies to increase physical activity in physical education lessons, student physical activity plans, and modification of school sport program); school environment (recess/lunchtime activities, school physical activity policy); parents (parent newsletters); and community (community physical activity provider promotion). Six additional strategies supported school implementation of the physical activity intervention strategies. Main outcome measure: Minutes per day spent in MVPA, objectively measured by accelerometer. Results: Participants (N¼1,150, 49% male) were a cohort of students aged 12 years (Grade 7) at baseline (March–June 2012) and 14 years (Grade 9) at follow-up (March–July 2014). At 24-month follow-up, there were significant effects in favor of the intervention group for daily minutes of MVPA. The adjusted mean difference in change in daily MVPA between groups was 7.0 minutes (95% CI¼2.7, 11.4, po0.002) (analysis conducted December 2014–February 2015). Sensitivity analyses based on multiple imputation were consistent with the main analysis (6.0 minutes, 95% CI¼0.6, 11.3, po0.031). Conclusions: The intervention was effective in increasing adolescents’ minutes of MVPA, suggesting that implementation of the intervention by disadvantaged schools has the potential to slow the decline in physical activity.