BACKGROUND/OBJECTIVES: To model the association between accumulating 60 daily minutes of moderate-to-vigorous physical activity and a composite score of biological risk factors into a direct and an indirect effect, using abdominal obesity as the mediator. SUBJECTS/METHODS: Cross-sectional data from the International Children's Accelerometry Database (ICAD) including 6-18-year-old children and adolescents (N=3412) from 4 countries providing at least 3 days of accelerometry-assessed physical activity. A standardized composite risk score was calculated from systolic blood pressure and fasting blood samples of insulin, glucose, triacylglycerol and inverse HDL-cholesterol. Abdominal obesity was assessed by the waist-circumference:height ratio. Two-stage regression analysis, allowing for exposure-mediator interaction, was used for the effect decomposition. RESULTS: Participants achieving 60 daily minutes of moderate-to-vigorous physical activity had a 0.31 (95% CI: -0.39, -0.23) standard deviations lower composite risk score than those achieving less than 60 min. Modelling the associations suggested that 0.24 standard deviations (95% CI: -0.32, -0.16) was attributed to the direct effect and -0.07 (95% CI: -0.11, -0.02) to the indirect effect indicating that 22% of the total effect was mediated by central adiposity. Modelling 30 and 90 min of moderate-to-vigorous physical activity per day resulted in changes in the direct but not the indirect effect. CONCLUSIONS: One hour of daily moderate-to-vigorous physical activity was associated with clinically relevant differences in metabolic control compared to engagement in less than this minimally recommended amount. The majority of the difference was explained by the direct effect of physical activity.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.241.