In animals, vegetable protein can inhibit gallstone formation. Epidemiologic studies of dietary protein in relation to gallstone disease are sparse, and the effects of dietary protein of different origins are not clear. The authors aimed to examine the relation between dietary protein intake and risk of cholecystectomy among participants in the Nurses’ Health Study, a cohort study of US women in 11 states. During 20 years of follow-up (1980–2000), the authors documented 7,831 cases of cholecystectomy. After adjustment for age, other known or suspected risk factors, and specific fats in a multivariate model, the relative risk of cholecystectomy for women in the highest quintile of dietary total protein intake compared with women in the lowest quintile was 1.00 (95% confidence interval (CI): 0.93, 1.08; p for trend=0.46). When extreme quintiles were compared, the relative risk for animal protein intake was 1.07 (95% CI: 0.98, 1.15; p for trend=0.08), whereas the relative risk for vegetable protein intake was 0.79 (95% CI: 0.71, 0.88; p for trend < 0.0001), with a significant dose-response relation. Additional mutual adjustment between animal and vegetable proteins did not materially alter the risks. These results suggest that increased consumption of vegetable protein in the context of an energy-balanced diet can reduce the risk of cholecystectomy in women.