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Previous small studies have shown either no difference or a lower risk of symptomatic gallstone disease in vegetarians than in non-vegetarians. This study examined the incidence of symptomatic gallstone disease in a cohort of British vegetarians and non-vegetarians, and investigated the associations between nutrient intake and risk of symptomatic gallstone disease.The data were analysed from 49 652 adults enroled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, one-third of whom were vegetarian. The linked databases of hospital records were used to identify incident cases. Risk by diet group was estimated using Cox proportional hazards models. Further analysis quantified risk by intakes of selected macronutrients.There were 1182 cases of symptomatic gallstone disease during 687 822 person-years of follow-up (mean = 13.85 years). There was a large significant association between increasing body mass index (BMI) and risk of developing symptomatic gallstone disease (overall trend P < 0.001). After adjustment for BMI and other risk factors, vegetarians had a moderately increased risk compared with non-vegetarians (HR: 1.22; 95% CI: 1.06-1.41; P = 0.006). Although starch consumption was positively associated with gallstones risk (P = 0.002 for trend), it did not explain the increased risk in vegetarians.There is a highly significant association of increased BMI with risk of symptomatic gallstone disease. After adjusting for BMI, there is a small but statistically significant positive association between vegetarian diet and symptomatic gallstone disease.