Background: ADIPOQ rs266729 have been associated with body mass index and metabolic parameters. Objectives: Our aim was to assess the contribution of this genetic variant on lipid profile and serum adiponectin levels after biliopancreatic diversion surgery in morbidly obese patients in a 3-year prospective study. Setting: Tertiary Hospital. Methods: A prospective cohort study (sample) of 149 patients with morbid obesity was evaluated. Biochemical and anthropometric parameters were studied at baseline and every year for a 3-year follow-up period. Results: Percentage of excess weight loss (65.9% versus 66.0%:ns), body mass index, weight, waist circumference, fat mass, blood pressure, fasting glucose, low-density lipoprotein cholesterol, total cholesterol, insulin, homeostasis model assessment of insulin resistance, and triglyceride levels improved in both genotype groups. A decrease in fasting insulin levels, homeostasis model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, and triglycerides was higher in non-G-allele carriers than G-allele carriers. The increase of adiponectin levels (at 1 yr) found after 1 (delta: 16.2 +/- 3.1 ng/mL versus 2.1 +/- 1.0 ng/mL; P=.02), 2 (delta: 24.2 +/- 3.1 ng/mL versus 3.1 +/- 1.1 ng/mL; P=.02), and 3 years (delta: 33.2 +/- 3.9 ng/mL versus 4.7 +/- 1.8 ng/mL; P=.01) was higher in non-G-allele carriers than G carriers. At all times, adiponectin levels were higher in patients with genotype CC. Conclusions: Non-G allele of ADIPOQ gene variant (rs266729) is associated with increases in adiponectin levels and better improvement of low-density lipoprotein cholesterol, triglycerides, insulin, and homeostasis model assessment of insulin resistance after biliopancreatic diversion massive weight loss than G-allele carriers. (C) 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.