Gallstone disease is a major source of morbidity in Western countries. Nuts are rich in several compounds that may be protective against gallstones. The objective of the study was to examine the relation between nut consumption and gallstone disease in the Health Professionals Follow-up Study. The consumption of nuts was assessed starting in 1986 as part of a 131-item semiquantitative food frequency questionnaire. The main outcome measure was newly diagnosed symptomatic gallstones. During 457,305 person-years of follow-up, 1,833 participants reported gallstone disease. After adjustment for age and other known or suspected risk factors, men consuming 5 or more units of nuts per week (frequent consumption) had a significantly lower risk of gallstone disease (relative risk = 0.70, 95% confidence interval: 0.60, 0.86; p(trend) < 0.001) than did men who never ate or who ate less than 1 unit per month (rare consumption) (1 unit = 1 ounce (0.028 kg) of nuts). Further adjustment for fat consumption (saturated fat, trans-fat, polyunsaturated fat, and monounsaturated fat) did not materially alter the relation. In analyses examining consumption of peanuts and other nuts separately, both were significantly associated with a lower risk of gallstone disease in the age-adjusted and multivariate models. Our findings suggest that frequent nut consumption is associated with a reduced risk of gallstone disease in men.