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Background Gallstone disease ( GD) incidence and prevalence rates differ between populations. Diet and lifestyle may be involved in GD development. To our knowledge, no study to date has evaluated quantitative data on diet when studying the relationship between fat consumption levels and GD in an Argentinean population. The present study aimed to assess the association between dietary fat intake and GD. Methods A nested case-control study design was applied. Data were taken from subjects who participated in a previous cross-sectional study carried out in a random sample of asymptomatic people in Rosario, Argentina. Participants underwent a personal interview, and current weight and height, ancestor's ethnicity, and socio-economic status were recorded. Applying a food-frequency questionnaire and a food photography atlas, quantitative dietary data were estimated by combining the intake frequency, portion size and food composition. Logistic regression analysis was used to compute odds ratios and 95% confidence intervals adjusted by age, sex, ancestor's ethnicity, body mass index and daily total energy intake as potential confounders. Results In total, 114 patients were studied (49 cases and 65 controls), without any statistically significant differences for age, sex, socio-economic status, body mass index and ancestry. The mean energy intake was higher in cases than in controls, and significant differences were found for dietary fat consumption. Obese or overweight people have a higher GD risk than subjects with normal weight. Increased GD risks were associated with high intakes of energy, total fat, and saturated and monounsaturated fatty acids. Conclusions According to our results, total fat, saturated and monounsaturated fatty acids high intakes are associated with increased GD risk. [ABSTRACT FROM AUTHOR]