Objective: To compare the efficacy and safety of laparoscopic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) and laparoscopic sleeve gastrectomy (SG) in the treatment of obesity and obesity-related metabolic diseases. Methods: A retrospective cohort study method was used to analyze the clinical data of 22 patients with obesity who underwent laparoscopic SADI-S in the China-Japan Union Hospital of Jilin university from May 2018 to December 2019 (SADI-S group). Meanwhile, 22 patients with obesity undergoing laparoscopic SG at the same period were selected in this study whose preoperative demographics, including sex, age, body weight, body mass index, metabolic diseases and blood index, were comparable to those of SADI-S group. All the patients were followed up at 3 months, 6 months and 12 months after operation to compare the weight loss [body weight, body mass index, percent of excess weight loss (%EWL) and percent of total weight loss (%TWL), etc.], remission of obesity-related metabolic diseases (hypertension, hyperuricemia, and type 2 diabetes mellitus, etc.) and nutritional deficiency (albumin, retinal-binding-protein, vitamin B12, vitamin D and iron protein, etc.) between the two groups. Results: All the patients successfully underwent laparoscopic bariatric surgery without conversion to laparotomy or death. Compared with SG group, SADI-S group had longer operative time [(204.8±38.3) minutes vs. (109.2±22.4) minutes, t=10.107, P<0.001], higher rate of intraoperative drainage tube [100.0% (22/22) vs. 50.0% (11/22), P<0.001], longer duration of indwelling drainage tube [4 (2-7) days vs. 1 (0-7) days, U=131.000, P=0.008], and the differences were statistically significant (all P<0.05). There was no significant difference between the SG group and the SADI-S group in terms of postoperative hospital stay and complication rate. The weight loss efficacy of SADI-S group and SG group was compared at 3, 6 and 12 months after operation. The results showed that with the increase of follow-up time, the patient's body weight and body mass index gradually decreased, %EWL and %TWL gradually increased (all P<0.05). There were no statistically significant differences in body weight, body mass index and %EWL between the SADI-S group and the SG group at 3, 6 and 12 months after operation (all P>0.05). There was no statistically significant difference of %TWL between two groups at 3 months after operation (F=0.846, P=0.368), but SADI-S group had higher %TWL at 6 and 12 months after operation and the differences were statistically significant (6-month: 34.0±5.1 vs. 30.2±4.3, F=5.813, P=0.025; 12-month: 42.9±6.8 vs. 34.8±7.6, F=14.262, P=0.001). Except for that the remission rate of total cholesterol of SADI-S group was higher than that of SG group, remission rates of metabolic diseases were not significantly different at different follow-up points (all P>0.05). As for the nutrient deficiency (albumin, retinal-binding-protein, iron protein, vitamin B12, vitamin D and folic acid) and the incidence of gallstones, no significant differences were found between two groups (all P>0.05). Conclusion: Both SADI-S and SG are safe and effective for the treatment of obesity and obesity-related metabolic diseases, but the former is more effective.