OBJECTIVE: To examine the relative importance of sedentarism and moderate-to-vigorous physical activity for adiposity development in children and adolescents. STUDY DESIGN: A total of 277 boys and 277 girls (95% white; two-thirds of parents with college graduation or higher education) from the Iowa Bone Development Cohort Study completed body fat and accelerometry measurement at examinations of 8, 11, 13, and/or 15 years of age (during 2000-2009). The main exposure was accelerometry-measured sedentary time, frequency of breaks in sedentary time, and moderate- to vigorous-intensity physical activity time. The outcome was dual energy x-ray absorptiometry-measured body fat mass. RESULTS: Adjusted for age, height, physical maturity, and sedentary time, growth models showed that high moderate-to-vigorous physical activity time was associated with low body fat mass in both boys (coefficient beta=-0.10+/-0.02) and girls (beta=-0.05+/-0.01; P<.01). However, sedentary time and frequency of breaks in sedentary time were not associated with body fat mass. CONCLUSIONS: This study does not support an independent effect of sedentarism on adiposity. The preventive effect of moderate- to vigorous-intensity physical activity on adiposity in children and adolescents remained strong after adjusting for the effect of sedentarism.