Gallstone disease (GSD) represents a significant health burden and is reported to be strongly related to obesity. This study examined the effect of sex on the association of BMI, waist circumference (WC) and percentage body fat mass (%FM) with GSD. We enrolled 15 671 middle-aged Taiwanese adults undergoing a physical check-up at a health examination centre. Multiple logistic regression analysis was conducted to identify the association of BMI, WC and %FM with the presence of GSD. AUC of the receiver–operating characteristic (ROC) curves were calculated for BMI, WC and %FM to compare their respective ability to correctly classify patients with GSD. From our findings, GSD prevalence was 8·1 % in men and 6·3 % in women. The percentage of markedly increased obesity indicators was significantly higher in patients with GSD than in those without GSD. Multivariate analysis showed that all obesity indicators were significant predictors of the presence of GSD in women after adjustment. In men, only BMI and WC were significantly associated with the presence of GSD. In the ROC curve analysis, BMI and WC were the best predictors of GSD risk in women and men, respectively. The obesity indicators better predicted the presence of GSD in women than in men. In conclusion, the best obesity indicator of GSD risk differed by sex. In addition to body weight, fat mass and central obesity were associated with GSD risk in women. In men, central obesity may play a more important role in predicting GSD risk.