OBJECTIVES: This study examined the correlates of clinical gallbladder disease among US adults and whether serum ascorbic acid levels are associated with a decreased prevalence of gallbladder disease. METHODS: Cross-sectional analyses of data from the Second National Health and Nutrition Examination Survey were conducted. RESULTS: A total of 384 women (8%) and 107 men (3%) reported a history of gallstone disease, and 347 women (7%) and 81 men (2%) reported a history of cholecystectomy. An inverted U-shaped relation was found between serum ascorbic acid level and clinical gallbladder disease among women but not among men. CONCLUSIONS: Ascorbic acid, which affects the catabolism of cholesterol to bile acids and, in turn, the development of gallbladder disease in experimental animals, may reduce the risk of clinical gallbladder disease in humans.