Background and aims: Obesity is a pandemic affecting approximately 700 million adults worldwide, with an additional 2 billion overweight. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic bariatric therapy that involves remodeling of the greater curvature in an effort to reduce gastric capacity and delay gastric emptying. A variety of ESG suture patterns has been reported. This study is the first to use a uniform « U » stitch pattern across all centers to simplify technical aspects of the procedure and limit cost. This also uniquely assessed outcomes in all body mass index (BMI) categories and changes in metabolic rate, lean body mass, and adipose tissue composition.Methods: This is a multicenter analysis of prospectively collected data from 7 centers including patients with overweight and obesity who underwent ESG. Primary outcomes included absolute weight loss, percent total body weight loss (%TWL), change in BMI, and percent excess weight loss (%EWL) at 6 and 12 months in overweight and obese classes I, II, and III. Secondary outcomes included adipose tissue, lean body mass reduction, and metabolic rate analyzed by bioimpedance. Additionally, immediate or delayed adverse events (AEs) were analyzed. Clinical success was defined as achieving ≥25% EWL at 1 year with ≤5% serious AE (SAE) rate following the American Society for Gastrointestinal Endoscopy (ASGE)/American Society for Metabolic and Bariatric Surgery (ASMBS) threshold.Results: A total of 193 patients underwent ESG during the study period. All groups had >10% TWL and >25% EWL at 6 months of follow-up. On average, %TWL was 14.25% ± 5.26% and 15.06% ± 5.22% and the %EWL 56.15% ± 22.93% and 59.41% ± 25.69% at 6 months and 1 year of follow-up, respectively. %TWL was 8.91% ± .3%, 13.92% ± 5.76%, 16.22% ± 7.69%, and 19.01% ± .95% and %EWL 56.21% ± 2.0%, 62.03% ± 27.63%, 54.13% ± 23.46%, and 46.78% ± 2.43% for overweight and obesity classes I, II, and III, respectively, at 1 year. Male sex, age <41 years, and higher BMI were predictors of achieving a TWL ≥10% at 1-year follow-up. There was a significant reduction in adipose tissue from baseline. SAEs occurred in 1.03%, including 2 perigastric collections needing surgery.Conclusions: ESG appears to be feasible, safe, and effective in the treatment of patients with overweight and obesity according to ASGE/ASMBS thresholds.