Humoral factors and neural mechanisms play a central role in the pathogenesis of obesity and in weight loss following bariatric surgery. Although various hormones and adipokines, including ghrelin and resistin, are linked to obesity, studies analyzing the changes in fasting ghrelin and resistin levels in patients following one anastomosis gastric bypass are lacking. We aimed to investigate resistin and ghrelin levels before and after two commonly used bariatric procedures with different mechanisms of action: sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB). Fasting serum ghrelin and resistin levels were evaluated by using ELISA in a non-randomized, prospective cohort study for the pattern of changes in the preoperative period and one week, one month, three months and, 12 months after surgery in age and sex-matched patients with BMI ≥40kg/m2 undergoing either sleeve gastrectomy (n=40) or one anastomosis gastric bypass (n=40). Their relationships with demographic parameters such as body weight, Body mass index (BMI), presence of T2DM, HbA1C, and HOMA-IR index were also evaluated. OAGB was superior in weight control compared to the SG group. There were significant differences in resistin and ghrelin levels between the OAGB and SG groups. Ghrelin decreased more in the SG group than the preoperative values. This change in ghrelin levels was more significant at one year after sleeve gastrectomy (preoperative mean(range) level of 334.2 (36.6-972.1) pg/mL decreased to 84 (9.1-227) pg/ml at one year) whereas in the OAGB group no significant change was observed (preoperative mean(range) level of 310 (146-548)pg/mL decreased to 264 (112-418)pg/mL at one year). Resistin levels decreased in both groups, especially after three months and onward following both operations (the mean(range) resistin levels were 2.6 (0.87-5.4)ng/mL and decreased to 1.1 (0.5-2.4)ng/mL in the SG group vs 2.48 (0.89-6.43)ng/mL decreased to 0.72 (0.35-1.8)ng/mL in OAGB group at one year), which was in parallel with changes in HOMA-IR index, body weight, and BMI changes at 1st year. HOMA-IR index changes were similar, but more prominent after OAGB. OAGB was also superior in T2DM control, parallel with weight loss, fasting resistin levels (especially after three months and onward), and HOMA-IR changes. This is the first study to compare fasting ghrelin and resistin levels after one anastomosis gastric bypass and sleeve gastrectomy. Although similar changes were observed, ghrelin changes were more prominent after SG, whereas resistin were observed after OAGB. OAGB was superior in T2DM control which was in parallel with weight loss, fasting resistin levels, and HOMA-IR changes suggesting a possible effect of resistin after OAGB in glucose metabolism and insulin resistance.