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Background Altered adiponectin levels are associated with metabolic abnormalities. The aim of this study was to explore the role of adiponectin in cholelithiasis. Methods A radioimmunoassay was used to determine serum adiponectin levels in 58 patients with cholesterol gallstones and 47 with pigment gallstones, and 101 healthy controls. The chemical composition of extracted gallstones was determined by Fourier transform infrared spectroscopy. Results The mean(s.d.) adiponectin level was decreased in patients with cholesterol gallstones (7·6(4·1) µg/ml; P < 0·001) but raised in patients with pigment gallstones (17·9(9·0) µg/ml; P < 0·001) in comparison with healthy controls (11·7(6·5) µg/ml). Decreased adiponectin levels (odds ratio (OR) 0·85 (95 per cent confidence interval (c.i.) 0·76 to 0·96); P = 0·008) and female sex (OR 6·06 (95 per cent c.i. 2·10 to 17·46); P = 0·001) were associated with cholesterol gallstone formation. Increased adiponectin levels (OR 1·11 (95 per cent c.i. 1·01 to 1·22); P = 0·025) and increased age (OR 1·06 (95 per cent c.i. 1·01 to 1·12); P = 0·029) were associated with pigment gallstone formation. Raised serum aspartate aminotransferase concentration was a risk factor for both cholesterol (OR 1·16 (95 per cent c.i. 1·03 to 1·30); P = 0·013) and pigment (OR 1·23 (95 per cent c.i. 1·10 to 1·38); P < 0·001) gallstones. Conclusion Gallstone formation is associated with altered serum adiponectin levels. Serum adiponectin might serve as a novel marker for cholesterol and pigment cholelithiasis.