The aim of this study was to verify whether a 1-year interdisciplinary weight-loss program improved common carotid artery intima-media thickness (IMT) and whether insulin resistance and/or inflammation (as measured by the markers plasminogen activator inhibitor type-1 and adiponectin) might underlie obesity in adolescents. A group of 29 post-pubescent obese adolescents were submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery IMT was determined ultrasonographically. Body composition, blood pressure (BP), glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile and adipokine concentrations were analyzed before and after the intervention. The interdisciplinary weight-loss program promoted a significant improvement in body composition, insulin concentration, HOMA-IR, lipid profile, BP and inflammatory state, in addition to significantly decreasing the common carotid artery IMT. Furthermore, this study demonstrated that the difference between baseline and final values of HOMA-IR (ΔHOMA-IR) was negatively correlated with concomitant changes in the adiponectin concentration (Δadiponectin; r=-0.42; P=0.02) and positively correlated with changes in common carotid artery IMT (Δcarotid IMT; r=0.41; P=0.03). Multiple regression analysis adjusted by age, cardiovascular risk factors and inflammatory markers showed that ΔHOMA-IR was an independent predictor of significant changes in common carotid artery IMT. This investigation demonstrated that an interdisciplinary weight-loss program promoted a reduction of the common carotid artery IMT in obese Brazilian adolescents, and the improvement of HOMA-IR was an independent predictor of carotid IMT changes in this population.