Background and Objective: Waist circumference (W) has been shown to be a good predictor of cardiovascular risk. The aim of this study was to investigate whether physical activity (PA) is related to W in adolescents as previously shown in adults. Design and Subjects: Cross-sectional population-based survey of 2714 12-y-old adolescents from the eastern part of France. MEASUREMENTS: Body mass index (BMI) and W were measured. Structured PA, active commuting to and from school and sedentary activities (SED), for example television viewing, computer/video games and reading and different potential confounders (dietary habits, parental overweight, family annual income tax and educational level) were assessed by a questionnaire. Results: The adolescents had a mean BMI of 19.0+/-3.4 kg/m(2), and 20.2% of them were overweight, with no gender difference. Boys had a greater W than girls (67.6+/-9.1 vs 65.7+/-8.9 cm, P<0.0001). In all, 42% of the girls and 25% of the boys did not practice any structured PA outside school and less than 40% of the adolescents commuted actively to school more than 20 min/day. About one-third of the adolescents devoted more than 2 h/day to SED. In univariate analyses, BMI was negatively associated with structured PA but significantly only for girls (P<0.01) and positively associated with SED for both genders (P<0.0001 for girls, P<0.01 for boys). W was negatively associated with structured PA and positively associated with SED both in girls (P<0.0001 and P=0.03, respectively) and boys (P<0.01 and P=0.08, respectively). Multiple general linear models show that SED is associated with BMI, independently of structured PA, in both genders. On the other hand, structured PA was inversely associated with W, independently of SED. The inverse relation between structured PA and W persisted after additional adjustment on BMI, with a greater effect of PA for the adolescents with higher BMI. Conclusions: In 12-y-old adolescents, structured PA is inversely associated with W, an indicator of total adiposity but also more specifically of abdominal fat. This suggests that PA may have a beneficial effect on youth metabolic and cardiovascular risks, in particular in the presence of overweight.