Technical Abstract: The purpose was to test for association between polymorphisms in the circadian clock-related gene PER2 and attrition in patients prone to withdrawal from a behavioral weight-reduction-program based on the Mediterranean Diet. 454 overweight/obese subjects (women= 380, men= 74), aged 20-65 years, who attended outpatient clinics specializing in obesity between January and December, 2008, were studied. Anthropometric, biochemical and dietary-intake variables were analyzed. Effectiveness of the program was assessed and a questionnaire of barriers to weight loss was considered. Multivariate analysis and logistic regression models were performed. Results indicate that PER2 polymorphisms rs2304672C>G and rs4663302C>T were associated with abdominal-obesity (P<0.05). Participants who withdrew from treatment were significantly more obese and had more barriers to lose weight (P<0.05). They also displayed a lower likelihood of “planning-eating in advance” and experiencing “stress with dieting” than those who completed treatment. Frequency of rs4663307 minor allele was significantly greater in withdrawers than in those who successfully completed treatment (P<0.05). Logistic regression analysis showed that rs2304672 C>G minor allele carriers had a greater probability of dropping out, displaying extreme snacking, experiencing stress with dieting, eating when bored and skipping breakfast than non-carriers. In conclusion, PER2 is implicated in attrition in weight loss treatment and may modulate eating behavior-related phenotypes. These findings could represent a step towards personalized health care and nutrition based on a combination of genotyping and psycho-behavioral characterization.