Background: While multidisciplinary weight loss (WL) programs have been suggested to improve the sensitivity of appetite control system, this study examined for the first time the effect of a specific multidisciplinary intervention on the hedonic aspects of food intake in adolescents with obesity.Study design: Twenty-four adolescents (11-15 years) with obesity (mean BMI: 35.7 ± 4.5 kg/m2; BMI percentile: 98.7 ± 0.5) took part in a 10-month inpatient WL program, which included physical activity, nutritional education and psychological support. Height, weight, body composition, food reward (pre- and post-meal), ad libitum energy intake, appetite sensations and eating behavior traits were assessed at baseline, 5 months and at the end of the 10-month intervention. Analyses were conducted with linear mixed models and paired t-tests.Results: The mean WL was 8.9 ± 6.9 kg. Appetite sensations and pre-meal hedonic ratings of liking for all food categories (HF: high-fat; LF: low-fat; SA: savory; SW: sweet) increased after 5 months (fasting hunger, p = 0.02; fasting desire to eat, p = 0.01; daily hunger, p = 0.001; pre-meal liking for HFSA, p = 0.03; LFSA, p = 0.04; HFSW, p = 0.009; LFSW, p = 0.005). In contrast, appetite sensations (fasting and daily), emotional eating (p < 0.001), uncontrolled eating (p = 0.009), and pre-meal explicit liking (for all food categories) decreased between months 5 and 10. Post-meal liking for HFSA (p < 0.001), LFSA (p = 0.002), HFSW (p = 0.02) and LFSW (p < 0.001) decreased between baseline and month 5 and remained unchanged between months 5 and 10.Conclusion: These findings suggest that adaptive mechanisms to WL occurring in the short-to-medium term are attenuated in the longer term with the persistence of WL. These results indicate improvements in the reward response to food in adolescents with obesity and may contribute to the beneficial effect of multicomponent WL interventions in this population. Future studies are required to confirm these findings and elucidate underlying mechanisms.