Background: The central melanocortin system modulates food intake and energy homeostasis. Melanocortin-4 receptor gene (MC4R) mutations are relatively common in monogenic severe obesity and have recently been associated with binge eating disorder (BED). The more prevalent proopiomelanocortin (POMC) and leptin receptor (LEPR) gene mutations are rarely associated with the obese phenotype or BED. It is not known whether MC4R/POMC/LEPR mutations or BED influence the outcome of dietary treatments of obesity. Gastric banding enforces a low calorie diet by diminishing the need for volitional adherence. Methods: The complete coding regions of MC4R, POMC and leptin-binding domain of LEPR were comparatively sequenced in 300 patients (233 women; age 42±1 years [mean±SEM]; BMI 43.5±0.3kg/m2) undergoing laparoscopic gastric banding. Eating behaviour, metabolic syndrome prevalence and postoperative weight loss and complications were compared between carriers and non-carriers of gene variants with and without BED during 36±3 months follow up. Results: Nineteen patients (6.3%) carried eight different MC4R mutation or variants; 85 (138) patients (48.9%, 79.3%) carried 13 (9) different POMC (LEPR) mutations. All MC4R mutation/variant carriers were bingers, compared to 18.1% of non-carriers (P<0.001), whilst POMC/LEPR mutation carriers and non-carriers demonstrated similar frequency (P>0.12). MC4R mutation carriers lost less weight (P=0.004, ANOVA for repeated measures) demonstrated less improvement of metabolic syndrome components (P=0.002 and had five times more gastric complications (P<0.001). All outcomes were similar among POMC/LEPR mutation carriers and non-carriers and MC4R non-carriers independent of BED. Conclusions: In conclusion, MC4R mutations and variants may predict outcome of dietary obesity treatment independent of binge eating disorder.