OBJECTIVES: To determine the role of physical activity intensity and bout-duration in modulating associations between physical activity and cardiometabolic risk markers. METHODS: A cross-sectional study using the International Children's Accelerometry Database (ICAD) including 38,306 observations (in 29,734 individuals aged 4-18 years). Accelerometry data was summarized as time accumulated in 16 combinations of intensity thresholds (≥500 to ≥3000 counts/min) and bout-durations (≥1 to ≥10 min). Outcomes were body mass index (BMI, kg/m2), waist circumference, biochemical markers, blood pressure, and a composite score of these metabolic markers. A second composite score excluded the adiposity component. Linear mixed models were applied to elucidate the associations and expressed per 10 min difference in daily activity above the intensity/bout-duration combination. Estimates (and variance) from each of the 16 combinations of intensity and bout-duration examined in the linear mixed models were analyzed in meta-regression to investigate trends in the association. RESULTS: Each 10 min positive difference in physical activity was significantly and inversely associated with the risk factors irrespective of the combination of intensity and bout-duration. In meta-regression, each 1000 counts/min increase in intensity threshold was associated with a -0.027 (95% CI: -0.039 to -0.014) standard deviations lower composite risk score, and a -0.064 (95% CI: -0.09 to -0.038) kg/m2 lower BMI. Conversely, meta-regression suggested bout-duration was not significantly associated with effect-sizes (per 1 min increase in bout-duration: -0.002 (95% CI: -0.005 to 0.0005) standard deviations for the composite risk score, and -0.005 (95% CI: -0.012 to 0.002) kg/m2 for BMI). CONCLUSIONS: Time spent at higher intensity physical activity was the main determinant of variation in cardiometabolic risk factors, not bout-duration. Greater magnitude of associations was consistently observed with higher intensities. These results suggest that, in children and adolescents, physical activity, preferably at higher intensities, of any bout-duration should be promoted.