Technical Abstract: Walking or bicycling to school, i.e. active commuting, has shown promise for improving physical activity and preventing obesity in youth. Our objectives were to examine, among US youth, whether active commuting was inversely associated with adiposity and positively associated with moderate-to vigorous physical activity (MVPA). We also examined whether MVPA mediated the relationships between active commuting and adiposity. Using data of participants aged 12-19 years from the US National Health and Nutrition Examination Survey 2003-2004 (n=789 unweighted), we constructed multiple linear regression models that controlled for dietary energy intake and socio-demographics. The main exposure variable was active commuting. The outcomes were BMI z-score, waist circumference, skinfolds and objectively measured MVPA. The product-of-coefficients method was used to test for mediation. Active commuting was inversely associated with BMI z-score (beta=-0.07, p=0.046) and skinfolds (beta=-0.06, p=0.029), and positively associated with overall daily (beta=0.12, p=0.024) and before- and after-school (beta=0.20, p<0.001) MVPA. Greater before- and after-school MVPA explained part of the relationship between active commuting and waist circumference (Sobel z=-1.98, p=0.048). Active commuting was associated with greater MVPA and lower measures of adiposity among US youth. Before- and after-school MVPA mediated the relationships between active commuting and waist circumference.