The objective of this study was to evaluate psychosocial and behavioral predictors of weight loss success in patients that are obese enrolled in a weight loss program. It was a quasi-experimental design, with a convenience sample (n=127) of men and women aged 21-75 years with BMI >30 kg/m2 enrolled in a medically supervised comprehensive clinic-based weight loss program. We performed assessments at baseline and after program completion via behavioral and psychosocial questionnaires exploring correlates of weight loss. The weight loss program included nutritional, physical and behavioral therapies. Surveys and scales assessed baseline major and daily life events as stressors that may affect weight loss. Pre-treatment perceived importance and actual engagement in weight loss behaviors - monitoring of eating behaviors, of meals and physical activity - also assessed. Multiple linear regression models were used, and an alpha (p-value) ≤0.05 determined statistical significance. Participants obtained clinically significant weight loss of 7% from baseline. Pretreatment engagement in weight loss behaviors (p<0.05) was a significant and independent predictor of weight loss; depression was negatively associated with weight loss (p<0.05). Major and daily stressors were not predictive of weight loss success. Baseline weight losing behaviors increase the likelihood of success; baseline depression decreases the likelihood of success in weight loss. Appropriate pre-treatment screening of behaviors and depression treatment may improve weight loss program success.