To assess the risk factors for symptomatic gallstones, 88,837 women in the Nurses' Health Study cohort (age range, 34 to 59 years) were followed for four years after completing a detailed questionnaire about food and alcohol intake in 1980. A total of 433 cholecystectomies and 179 cases of newly symptomatic, unremoved gallstones, diagnosed by ultrasonographic examination or x-ray films, were reported during the four-year follow-up. The age-adjusted relative risk for very obese women, who had a Quetelet index of relative weight (weight in kilograms divided by the square of the height in meters) of more than 32 kg per square meter, was 6.0 (95 percent confidence interval, 4.0 to 9.0), as compared with women whose relative weight was less than 20 kg per square meter. For slightly overweight women (relative weight, 24 to 24.9 kg per square meter), the relative risk was 1.7 (95 percent confidence interval, 1.1 to 2.7). Overall, we observed a roughly linear relation between relative weight and the risk of gallstones. Among the 59,306 women whose relative weight was less than 25 kg per square meter, a high energy intake (>8200 J per day), as compared with a low energy intake (<4730 J per day), was associated with an increased incidence of symptomatic gallstones (relative risk, 2.1; 95 percent confidence interval, 1.4 to 3.3), and an alcohol intake of at least 5 g per day was associated with a decreased incidence as compared with abstention (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.8). Parity did not appear to be an important risk factor after an adjustment was made for relative weight. These data support a strong association between obesity and symptomatic gallstones and suggest that even moderate overweight may increase the risk. (N Engl J Med 1989;321:563–9.), THE incidence and prevalence of cholelithiasis vary greatly among geographic regions and ethnic groups.1,2 The prevalence of gallstones at autopsy ranges from 44 percent in Malmö, Sweden, to 5 percent in Lisbon, Portugal.2 Some of this variation is due to the occurrence of two distinct types of gallstones that differ in composition and presumably in pathogenesis: the comparatively unpigmented “cholesterol stones” and “pigmented stones,” containing bilirubin.3 In Japan, in the 1950s, pigmented stones predominated and cholesterol stones were rare, but by the early 1970s, the incidence of cholesterol stones surpassed that of pigmented stones by 50 percent.4 In the United….