The prevalence of obesity is increasing worldwide. Previous research has shown a relationship between obesity and both executive functioning alterations and frontal cortex volume reductions. The Brain Derived Neurotrophic Factor val66met polymorphism, involved in eating behavior, has also been associated with executive functions and prefrontal cortex volume, but to date it has not been studied in relation to obesity. Our aim is to elucidate whether the interaction between the Brain Derived Neurotrophic Factor val66met polymorphism and obesity status influences executive performance and frontal-subcortical brain structure. Sixty-one volunteers, 34 obese and 27 controls, age range 12–40, participated in the study. Participants were assigned to one of two genotype groups (met allele carriers, n = 16, or non-carriers, n = 45). Neuropsychological assessment comprised the Trail Making Test, the Stroop Test and the Wisconsin Card Sorting Test, all tasks that require response inhibition and cognitive flexibility. Subjects underwent magnetic resonance imaging in a Siemens TIM TRIO 3T scanner and images were analyzed using the FreeSurfer software. Analyses of covariance controlling for age and intelligence showed an effect of the obesity-by-genotype interaction on perseverative responses on the Wisconsin Card Sorting Test as well as on precentral and caudal middle frontal cortical thickness: obese met allele carriers showed more perseverations on the Wisconsin Card Sorting Test and lower frontal thickness than obese non-carriers and controls. In conclusion, the Brain Derived Neurotrophic Factor may play an important role in executive functioning and frontal brain structure in obesity. © 2014 Wiley Periodicals, Inc.