Aims: To compare economic and clinical outcomes between patients undergoing laparoscopic Rouxen-Y gastric bypass (LRY) or laparoscopic sleeve gastrectomy (LSG) with use of powered vs manual endoscopic surgical staplers. Materials and methods: Patients (aged !21 years) who underwent LRY or LSG during a hospital admission (January 1, 2012-September 30, 2015 were identified from the Premier Perspective Hospital Database. Use of powered vs manual staplers was identified from hospital administrative billing records. Multivariable analyses were used to compare the following outcomes between the powered and manual stapler groups, adjusting for patient and hospital characteristics and hospital-level clustering: hospital length of stay (LOS), total hospital costs, medical/surgical supply costs, room and board costs, operating room costs, operating room time, discharge status, bleeding/transfusion during the hospital admission, and 30, 60, and 90-day all-cause readmissions. Results: The powered and manual stapler groups comprised 9,851 patients (mean age ¼ 44.6 years; 79.3% female) and 21,558 patients (mean age ¼ 45.0 years; 78.0% female), respectively. In the multivariable analyses, adjusted mean hospital LOS was 2.1 days for both the powered and manual stapler groups (p ¼ .981). Adjusted mean total hospital costs ($12,415 vs $13,547, p ¼ .003), adjusted mean supply costs ($4,629 vs $5,217, p ¼ .011), and adjusted mean operating room costs ($4,126 vs $4,413, p ¼ .009) were significantly lower in the powered vs manual stapler group. The adjusted rate of bleeding and/or transfusion during the hospital admission (2.46% vs 3.22%, p ¼ .025) was significantly lower in the powered vs manual stapler group. The adjusted rates of 30, 60, and 90-day all-cause readmissions were similar between the groups (all p > .05). Sub-analysis by manufacturer showed similar results. Limitations: This observational study cannot establish causal linkages. Conclusions: In this analysis of patients who underwent LRY or LSG, the use of powered staplers was associated with better economic outcomes, and a lower rate of bleeding/transfusion vs manual staplers in the real-world setting.ARTICLE HISTORY