The majority of adults in the United States have overweight or obesity which is associated with significant health and psychological consequences. Behavioral Weight Loss (BWL) is the current gold-standard weight-loss program for adults but recidivism rates continue to be disturbingly high. Given the health consequences of excess weight and the lack of long-term effectiveness of BWL, it is important to identify novel weight-loss programs. We developed the ROC (Regulation of Cues) program to reduce overeating through improvement in sensitivity to appetitive cues and decreased responsivity to external food cues. This study is a 4-arm randomized control trial designed to evaluate the efficacy of ROC, ROC combined with BWL, BWL alone and an active comparator over 24 months. Study recruitment completed in November 2017. Two hundred and seventy-one participants were randomized (mean age = 46.97 years; 82% female, mean BMI = 34.59; 20% Hispanic) and assessments were conducted at baseline, mid-treatment (6 months) and post-treatment (12 months). At this time, participants are completing 6- (18 months) and 12-month (24 months) follow-ups. Targeting novel mechanisms is critically important to improve weight-loss programs. Through this trial, we hope to identify treatments for adults with overweight and obesity to facilitate long-term weight loss and improved health