Objectives: This study compared a behavioral weight loss program (BWL) with a stress management-based program, Emotional Brain Training (EBT), on weight loss, blood pressure, depression, perceived stress, diet, and physical activity. Methods: Subjects with a body mass index (BMI) of >28 and <45 kg/m(2) were recruited in Lexington, Kentucky in January 2014 and randomized to BWL or EBT for a 20-week intervention. Of those recruited, 49 participants were randomized to EBT or BWL. Randomization and allocation to group were performed using SPSS software. Weight, blood pressure, depression, perceived stress, dietary intake, and physical activity were measured at baseline, 10 week, and 20 week. Linear models for change over time were fit to calculate 95% confidence intervals of intervention effects. Results: BWL produced greater changes in BMI than EBT at both 10 (P = 0.02) and 20 wk (P = 0.03). At 10 wk, both EBT and BWL improved BMI, systolic blood pressure, depression and perceived stress (P < 0.05). BWL also improved diastolic blood pressure (P = 0.005). At 20 wk, EBT maintained improvements in BMI, systolic blood pressure, depression, and perceived stress while BWL maintained improvements only in BMI and depression (P < 0.05). Conclusions: BWL produced greater weight loss than EBT; however, EBT produced sustained improvements in stress, depression, and systolic blood pressure. A combination of the two approaches should be explored. (C) 2016 Elsevier Inc. All rights reserved.