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Background: The aim of this study was to determine the effects of a 12-month healthy lifestyle intervention based on diet plus physical activity on cardiovascular structure and function in children and adolescents with obesity; Methods: In this longitudinal study we assessed changes in anthropometric, biochemical and cardiovascular variables in 55 subjects with obesity (6–16 years) before and after a 12-month behavioral program based on Mediterranean diet plus exercise regimen. Subjects were divided in two groups based on negative change in BMI z-score ≥10% from baseline: weight losers (WL) and non-weight losers (NWL); Results: After 12 months, WL showed a significant improvement of metabolic parameters. Treatment was effective in increasing the mitral peak early diastolic velocity E and the E/A ratio. In subjects with a reduction of the number of NCEP-ATPIII metabolic syndrome criteria, lifestyle intervention reduced left ventricular area and volume. Intervention reduced carotid intima-media thickness in subjects showing a decrease of the systemic blood pressure; Conclusions: In children with obesity, cardiovascular impairment could be partially reversed by a healthy lifestyle intervention. To adopt prompt behavioral programs in childhood obesity is crucial both for prevention and treatment of precocious complications and could have an exponential impact on long-term morbidity and mortality.