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Sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are among the commonly performed bariatric procedures. This randomized study aimed to compare SG and OAGB in terms of weight loss, improvement in comorbidities, and change in serum ghrelin and glucagon-like peptide-1 (GLP-1) levels.This was a prospective randomized trial on patients with morbid obesity associated with medical comorbidities who were randomly assigned to 1 of 2 equal groups; group I underwent SG and group II underwent OAGB. Outcome measures were percent of excess weight loss (%EWL), improvement in comorbidities, change in the venous levels of fasting ghrelin and postprandial GLP-1 at 12 months after surgery, in addition to operation time and complications.Forty patients (38 female) of a mean age of 33.8 years and mean body mass index of 48.6 kg/m2 were included. Operation time in group II was significantly longer than in group I (86 vs. 52.87 min; P<0.001). There were 6 recorded complications (1 in group I and 5 in group II, P=0.18). The %EWL, %total weight loss, and %excess body mass index loss at 6 and 12 months postoperatively were significantly higher in group II than in group I. Both groups had similar rates of improvement in comorbidities. Group I had significantly lower ghrelin and GLP-1 levels postoperatively at 6 and 12 months, respectively, as compared with group II.OAGB was associated with significantly higher EWL than SG. The reduction in fasting ghrelin and postprandial GLP-1 serum levels at 12 months after SG was significantly higher than that after OAGB.