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Objectives: To explore the relationship between the blood group of patients and their response to bariatric surgery and to identify predictors of better outcomes. Methods: This was a retrospective cross-sectional analysis of patients who underwent laparoscopic sleeve gastrectomy for morbid obesity between 2014 and 2020 at King Saud University Medical City in Riyadh, Saudi Arabia. Results: This study included 1434 individuals. The mean change in BMI (pre- versus post-BMI) differed statistically significantly between blood groups (p ≤ 0.01). The greatest drop in body weight was seen in individuals with the AB-negative blood type (56.0 (21.4) kg), which corresponds to the greatest percentage of reduction from baseline (47.7% (14.8)). The mean BMI of the patients decreased by 34.7% (9.2) from a mean pre-operation BMI of 45.5 (8.4) kg/m2 to 29.7 (6.1) kg/m2 (p ≤ 0.001). After laparoscopic sleeve gastrectomy, male patients and those with the B-negative blood type are more likely to see a greater BMI reduction (pre-operation compared to post-operation) (p ≤ 0.05). Conclusions: For morbidly obese patients, laparoscopic sleeve gastrectomy demonstrated promising weight loss outcomes. Blood groups may be able to predict the success rate of bariatric surgery in morbidly obese patients.