The aim of this study was to evaluate the effect of an intervention targeting the physical and organizational school environment for noncurricular physical activity (SPACE) on adiposity, aerobic fitness, and musculo-skeletal strength in Danish adolescents. The study used a cluster randomized controlled design. Fourteen schools and 1348 adolescents aged 11-14 years were included at baseline. Seven schools were randomized to the intervention, which was designed to change the organizational and physical environment of the school. The analysis revealed no significant differences between the adolescents in the intervention group compared to the comparison group after a 2-year follow-up. Adjusted for baseline, sex, age, and clustering within schools, the difference between the intervention schools compared to the comparison schools was 6 m in the shuttle run test [95% confidence interval (CI): -21; 33], 0.2 cm in waist circumference (95% CI: -2.6; 3.1), and -1.1 kg in handgrip strength (95% CI: -2.2; -0.1). The results did not provide evidence for the effect of the intervention on adiposity, aerobic fitness, or musculo-skeletal strength in adolescents. Reasons for not finding an effect could be related to both the design and the implementation of the intervention.