Cholesterol gallstone disease is often associated with the metabolic syndrome. Female gender is an unmodifiable risk factor for cholelithiasis and, in its turn, the metabolic syndrome features a sexual dimorphism which warns that a global approach might overlook important discrimination. We carried out a retrospective analytical case-control study in order to perform a comparative analysis between two groups of female patients with metabolic syndrome and gallstones (n=60) or without gallstones (n=65). All the patients were investigated by abdominal ultrasound and met at least three criteria for the diagnosis of metabolic syndrome. Cases and controls were compared regarding anthropometric measurements, a complex lipid profile, and liver function tests. The risks associated with the likelihood of gallstones were estimated by means of cross-tabulation. In order to rank the significant variables we developed a binary logistic regression model which identified lean body weight ≤ 46.44 kg (OR 0.165; 95% CI 0.045–0.611; P = 0.007), total cholesterol ≥ 4.9 mmol/L (OR 15.948; 95% CI 2.700–94.205; P = 0.002), and direct bilirubin > 5.1 µmol/L (OR 0.056; 95% CI 0.013–0.235; P < 0.001), as variables with significant probability of association with the risk of gallstones in women with metabolic syndrome.