Purpose: Biliopancreatic diversion with duodenal switch and single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) are technically demanding hypo-absorptive bariatric procedures generally indicated in super-obese patients (BMI ≥ 50 kg/m²). Data from the literature prove the procedure to be safe and effective, with promising bariatric and metabolic effects. Anyway, international societies support the creation of multicentric national and international registries to obtain more homogeneous data over the long period. We aimed to report our experience with this procedure. Methods: Among 2313 patients who underwent bariatric procedures at our institution, between July 2016 and August 2021, 121 (5.2%) consenting patients were scheduled for SADI-S as primary (SADIS) or revisional procedure after sleeve gastrectomy (SADI) (respectively 87 and 34 patients). Early and late post-operative complications, operative time, post-operative stay, and follow-up data were analyzed. Results: Overall, the median preoperative BMI was 52.3 (48.75–57.05) kg/m² with a median age of 44 (39–51) years, the median operative time was 120 (100–155) min. Complications at 30th-day post-op were registered in 4 (3.3%) patients and late complications in 4 (3.3%) patients. At a median follow-up of 31 (14–39) months, the median percentage excess weight loss was 79.8 (55.15–91.45)%, and the median total weight loss was 57.0650 (43.3925–71.3475)%. Conclusion: Our data, coherently with the literature, confirm that SADI-S is a safe, effective procedure with acceptable complications rate. Larger studies with longer follow-ups are necessary to draw definitive conclusions.