Abstract Bariatric surgery is currently the most efficacious and durable intervention for severe obesity. Many comorbid conditions (e.g., diabetes, hypertension) generally remit or resolve following bariatric surgery. Yet, some patients experience suboptimal weight outcomes following surgery, often resulting from substantial weight regain following successful weight loss. Unfortunately, weight recidivism is also often associated with reemergence of obesity-associated comorbidities. The most commonly performed procedures in the U.S. are the Roux-en-Y Gastric Bypass (RYGB) and the laparoscopic Sleeve Gastrectomy (SG). Both procedures involve significant anatomical and physiological changes that lead to changes in behavior and biology. The etiological contributors to weight loss following surgery are not well understood, and it is therefore difficult to predict which patients may experience suboptimal post-surgical weight outcomes. Changes in eating and physical activity behaviors, mood, and the microbiome have all been reported to occur following bariatric surgery and have an association with weight change. Weight change likely involves complex interactions between behavioral and biological variables. The longitudinal relationship between changes in the gut microbiome and post-surgery weight trajectory has not been explored thoroughly, and the associations between the microbiome and other variables that impact weight have been similarly understudied. Therefore, we propose to conduct a prospective, 24-month longitudinal study of patients planning to undergo RYGB or SG and aim to identify correlates and predictors of observed weight loss trajectories over 24 months following bariatric surgery. In particular, this application is designed to examine the relationships between empirically supported behavioral and biological variables following surgery and their combined impact on weight outcome. These data will extend the current literature by collecting behavioral and biological data, by carrying out longer term follow-up of participants enrolled, and by studying a larger sample size. Novel data collection in this protocol will include intensive measurement of problematic eating behaviors and compliance with diet and exercise regimens post-surgically, which may be altered in parallel with, or in response to, changes observed in the gut microbiota. Identifying post-surgical predictors of weight loss and comorbidity resolution will allow for the development of interventions that can be tailored to individual patients based upon his/her risk profile which can then be implemented early to optimize surgery-related outcomes.