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Background: Recent research has described that obesity and high carbohydrates intake increases fat content of the gallbladder, decreases its motility and mucosal absorption, leading to a condition known as steatocholecystitis. Gallstone disease (GD) and the metabolic syndrome (MS) share common risk factors. Objective: To identify if MS contributes to the development of functional disorders and wall changes of the gallbladder. Methods: A Prospective study was conducted from August 2010 to July 2011 on patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy. Forty two patients were included and divided into two groups; 22 patients with MS and 20 patients without MS. Family history, risk factors, anthropometric, clinical and laboratory variables were evaluated before surgery. Gallbladder specimens were analyzed, measured and graded by two pathologists at 3 standardized areas (cystic duct, liver bed, free margin and fundus). Results: Thirty three patients who underwent cholecystectomy were female. A family history of GD and MS were present in 90% of patients. Chronic cholecystitis was the most frequent diagnostic (93%). Median weight was 75.5kg±14.3 and 67.1kg±9.2 for MS and No-MS groups respectively. Gallbladder wall thickness was significantly increased (P=0.012) in the MS group. This thickness was secondary mainly observed in the cystic duct area of patient with MS. The percentage of fatty infiltration of the gallbladder wall, muscle degeneration and cholesterolosis did not show significant differences between groups. Conclusions: MS is associated with an increased gallbladder wall thickness. Muscle fibrosis in the cystic duct was the most important wall modification in these patients. In our series, MS was not associated to fat infiltration of the gallbladder wall or cholesterolosis.