['Gallstones are common and contribute to morbidity and health care costs, but their effects on mortality are unclear. We examined whether gallstone disease was associated with overall and cause-specific mortalities in a prospective national population-based sample.', 'We analyzed data from 14,228 participants in the third US National Health and Nutrition Examination Survey (20-74 years old) who underwent gallbladder ultrasonography from 1988 to 1994. Gallstone disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. The underlying cause of death was identified from death certificates collected through 2006 (mean follow-up, 14.3 years). Mortality hazard ratios (HR) were calculated using Cox proportional hazards regression analysis to adjust for multiple demographic and cardiovascular disease risk factors.', 'The prevalence of gallstones was 7.1% and of cholecystectomy was 5.3%. During a follow-up period of 18 years or more, the cumulative mortality was 16.5% from all causes (2389 deaths), 6.7% from cardiovascular disease (886 deaths), and 4.9% from cancer (651 deaths). Participants with gallstone disease had higher all-cause mortality in age-adjusted (HR = 1.3; 95% confidence interval [CI]: 1.2-1.5) and multivariate-adjusted analysis (HR = 1.3; 95% CI: 1.1-1.5). A similar increase was observed for cardiovascular disease mortality (multivariate-adjusted HR = 1.4; 95% CI: 1.2-1.7), and cancer mortality (multivariate-adjusted HR = 1.3; 95% CI: 0.98-1.8). Individuals with gallstones had a similar increase in risk of death as those with cholecystectomy (multivariate-adjusted HR = 1.1; 95% CI: 0.92-1.4).'] Is gallstone disease associated with increased mortality in the United States?