Purpose: Many unhealthy behavioral habits often originate in adolescence. In the literature, the school-based whole school approach is stated be the most promising way to promote healthy behavior. Herein, interventions are evidence based and integrated into the curriculum, while embedded in complementary healthy school policies and environment. This study evaluates the effects of such an intervention on Dutch high schools. Methods: Two Dutch high schools and two controls were followed to evaluate the intervention’s effects on health behaviors, body mass index, and psychosocial problems after 1 year (N = 969) and 2 years (N = 605). Outcomes were measured via self-report surveys and analyzed with mixed methods regression analyses. To complement information on intervention effects, structured interviews were held with a representative sample of teachers per intervention school to map their respective whole school approach implementation success. Results: After 2 years, one intervention school showed significant improvements: Body mass index and excessive screen time use were reduced. In the other intervention school, priority targets did not improve. These findings reflected their respective success in intervention implementation, for example, differences in intervention integration and tailoring. Conclusions: This study shows that it is feasible for schools to implement a comprehensive Health Promoting School intervention themselves and that, when successful, effects in terms of improving behaviors and health outcomes are promising. The process evaluation helped understand these findings in context.