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Introduction: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S), like other hypoabsorptive procedures, could be burdened by long-term nutritional deficiencies such as malnutrition, anemia, hypocalcemia, and hyperparathyroidism. Objectives: We aimed to report our experience in terms of mid-term (2 years) bariatric, nutritional, and metabolic results in patients who underwent SADI-S both as a primary or revisional procedure. Methods: One hundred twenty-one patients were scheduled for SADI-S as a primary or revisional procedure from July 2016 to February 2020 and completed at least 2 years of follow-up. Demographic features, bariatric, nutritional, and metabolic results were analyzed during a stepped follow-up at 3 months, 6 months, 1 year and 2 years. Results: Sixty-six patients (47 female and 19 male) were included. The median preoperative BMI was 53 (48–58) kg/m2. Comorbidities were reported in 48 (72.7%) patients. At 2 years, patients had a median BMI of 27 (27–31) kg/m2 (p < 0.001) with a median %EWL of 85.3% (72.1–96.1), a TWL of 75 (49–100) kg, and a %TWL of 50.9% (40.7–56.9). The complete remission rate was 87.5% for type 2 diabetes mellitus, 83.3% for obstructive sleep apnea syndrome and 64.5% for hypertension. The main nutritional deficiencies post SADI-S were vitamin D (31.82%) and folic acid deficiencies (9.09%). Conclusion: SADI-S could be considered as an efficient and safe procedure with regard to nutritional status, at least in mid-term (2 years) results. It represents a promising bariatric procedure because of the excellent metabolic and bariatric outcomes with acceptable nutritional deficiency rates. Nevertheless, larger studies with longer follow-ups are necessary to draw definitive conclusions.