Background <p>Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-S) has gained increasing popularity in bariatric surgery due to its promising weight loss and metabolic outcomes. However, long-term evidence remains limited. This systematic review aimed to assess the 5-year outcomes of SADI-S performed as a primary bariatric procedure, focusing on weight loss, morbidity, mortality, and complications.</p> Methods <p>A systematic literature search was conducted in accordance with PRISMA guidelines. Out of 13 studies identified, four met the inclusion criteria. These studies reported outcomes of SADI-S as a primary bariatric procedure with follow-up at 5 years.</p> Results <p>The included studies comprised 1088 patients across four centers. The mean preoperative BMI was 49.66 kg/m², with women representing 64% of the cohort. At 5 years, follow-up data were available for 326 patients. The procedure demonstrated sustained weight loss, with a mean total weight loss (TWL) of 33.67% and excess weight loss (EWL) of 72.88%, resulting in a mean BMI of 31.7 kg/m². Short-term complication rates ranged from 5.4% to 11.6%, while long-term complications ranged from 8.7% to 17.9%. Malnutrition-related reoperations were associated with a common channel length of 200 cm. Mortality rates were consistently low.</p> Conclusions <p>SADI-S appears to be an effective bariatric procedure, providing sustained weight loss and acceptable complication rates at 5 years. Its safety profile is comparable to other bariatric techniques. Nonetheless, nutritional risks—particularly those related to protein malnutrition—highlight the importance of structured postoperative monitoring. Further prospective studies are needed to validate these findings and guide surgical decision-making.</p>