Background: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modification of the classic duodenal switch (DS). These modifications are intended to address concerns about DS, including malnutrition, longer operative times, and technical challenges, while preserving the benefits. Objectives: To evaluate safety and outcomes of SADI-S as it compares to classic DS procedure. Setting: Bariatric Surgery Center of Excellence, University Hospital, Montreal, Canada. Methods: In a single-institution prospective cohort study, we compared safety and outcomes of the SADI-S versus DS procedures (ClinicalTrials.gov: NCT02792166; registered: 06/2016). Data is depicted as count (percentage) or median (interquartile range). Results: There were 42 patients who underwent SADI-S, of whom 11 had it as a second-stage procedure (26%). There were 20 patients who underwent DS, of whom 12 had it as second-stage procedures (60%). Both groups were similar at baseline. Themedian age was 45 (14) years, 39 (63%) were female, themedian body mass index (BMI) was 48.2 (7.7) kg/m(2), and 29 (47%) patients had diabetes. The operative time was shorter for 1-stage SADI-S versusDS surgery (211 [70] versus 250 [60] min, respectively; P = .05) but was similar for second-stage procedures (P = .06). The 90-day complication rates were 11.9%(N = 5/42) after SADI-S and 5.0% (N = 1/20) afterDS surgery (P = .64). There were no mortalities. Median follow-ups for 1-stage SADI-S and DS were 17 (11) and 12 (24) months, respectively (P 5.65). Similar BMI changes were observed after 1-stage SADI-S (17.9 kg/m(2) [8.7]) and DS (17.5 kg/m(2) [16]; P = .65). At median follow-ups of 10 (20) and 14 (16) months after second-stage SADI-S and DS, respectively (P = .53), surgical procedures yielded added 5.0 kg/m(2) (5.8) and 6.5 kg/m(2) (7.1) changes in BMI, respectively (P = .26). Complete remission rates for diabetes were 91% after SADI-S (n = 21/23) and 50% after DS (n 5 3/6). Compared with the SADI-S procedure, DS surgery was associated with higher frequencies of deficiencies in some fat-soluble vitamins, especially vitamin D. Conclusions: The SADI-S procedure is safe, and its short-term outcomes, including weight loss and the resolution of co-morbidities, are similar to those of DS. SADI-S surgery also has promising potential as a second-stage procedure after sleeve gastrectomy. (C) 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.