Objective To develop a model to assess the long-term costs and health outcomes of physical activity interventions targeting adolescents. Design A Markov cohort simulation model was constructed with the intention of being capable of estimating long-term costs and health impacts of changes in activity levels during adolescence. The model parameters were informed by published literature and the analysis took a National Health Service perspective over a lifetime horizon. Univariate and probabilistic sensitivity analyses were undertaken. Setting School and community. Participants A hypothetical cohort of adolescents aged 16 years at baseline. Interventions Two exemplar school-based: A comparatively simple, after-school intervention and a more complex multicomponent intervention compared with usual care. Primary and secondary outcome measures Incremental cost-effectiveness ratio as measured by cost per quality-adjusted life year gained. Results The model gave plausible estimates of the long-term effect of changes in physical activity. The use of two exemplar interventions suggests that the model could potentially be used to evaluate a number of different physical activity interventions in adolescents. The key model driver was the degree to which intervention effects were maintained over time. Conclusions The model developed here has the potential to assess long-term value for money of physical activity interventions in adolescents. The two applications of the model indicate that complex interventions may not necessarily be the ones considered the most cost-effective when longer-term costs and consequences are taken into account.