Background <p>Evaluate and compare the results of weight loss outcomes, associated medical problems resolution, and complications in the short and long term between SADI-S and RYGB.</p> Methods <p>A systematic review was conducted following PRISMA guidelines. Studies comparing SADI-S and RYGB as primary surgery were included if they reported weight loss (total weight loss (TWL), excess weight loss (EWL), or body mass index (BMI) changes), associated medical problems remission (diabetes and hypertension), and postoperative outcomes (complications, hospital stay, and operative time). A meta-analysis of mean differences (MD) was conducted to assess continuous outcomes, and a meta-analysis of odds ratios (OR) was performed to evaluate the categorical variables; a random effects model was used.</p> Results <p>Eight studies, including 4259 patients (1625 SADI-S; 2634 RYGB), were analysed. Six studies with over 2&#xa0;years of follow-up (mean 3.93&#xa0;years (1.79)) were included for long-term outcomes, while all eight were considered for short-term outcomes. SADI-S resulted in a statistically significant higher total weight loss (MD 10.03; 95% CI 4.7–15.35; <i>p</i> &lt; 0.001), excess weight loss (MD 10.15; 95% CI 5.2–15.1; <i>p</i> &lt; 0.01), diabetes remission (OR 3.48; 95% CI 2.02–6.02; <i>p</i> &lt; 0.001) with a similar number of long-term complications (OR = 0.19, 95% CI 0.03–1.36; <i>p</i> = 0.10). Short-term complications were inferior in the subgroup of patients undergoing SADI-S with &lt; 50&#xa0;kg/m² of BMI (OR 0.45, 95% CI 0.33 to 0.61; <i>p</i> &lt; 0.01) as well as hospital stay (MD = –0.69; 95% CI –1.03 to –0.36, <i>p</i> &lt; 0.01) and severe complications (OR = 0.44, 95% CI 0.25–0.80; <i>p</i> = 0.01).</p> Conclusions <p>This meta-analysis suggests that SADI-S may offer advantages over RYGB in terms of weight loss, diabetes remission, and safety profile.</p>