Background: Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective yet technically challenging bariatric surgery with many complications. Alternatively, single anastomosis duodenalileal bypass with sleeve gastrectomy (SADI-S) was recently introduced as a simplified bariatric procedure. This meta-analysis aimed to assess the safety and efficacy of SADI-S compared with BPD-DS in the management of patients with obesity.Methods: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to May 2022 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis system. The review was registered prospectively with PROSPERO (CRD42022333521).Results: From 123 studies screened, 6 studies met the eligibility criteria, with a total of 1847 patients with obesity undergoing either SADI-S (n = 818) or BPD-DS (n = 1029). Preoperative body mass index was similar between the 2 groups, and the BPD-DS group had a greater % excess body mass index loss (EBMIL) (MD = −10.16%, 95% confidence interval: −11.80, −8.51, I 2 = 0%) at 2 years compared with the SADI-S group. There was no difference observed in preoperative comorbidities and remission, including diabetes, hypertension, and dyslipidemia between SADI-S and BPD-DS cohorts. Compared with BPD-DS, SADI-S had shorter hospital stays (MD = −1.36 d, 95% CI: −2.39, −0.33, I 2 = 86%), and fewer long-term ( > 30 d) complications (OR = 0.56, 95% CI: 0.42, 0.74, I 2 = 20%). Conversely, among nutritional deficiency outcomes, the SADI-S group had few patients with abnormal vitamin D (OR = 0.51, 95% CI: 0.36, 0.72, I 2 = 0%) values than the BPD-DS group.Conclusions: SADI-S has shown to be a possible alternative treatment option to BPD-DS in managing patients with obesity. Despite the promising results, further randomized controlled studies with more extended follow-up periods are necessary to ascertain the safety and efficacy of the treatment.