Chile's gallbladder cancer rates are among the highest in the world, being the leading cause of cancer deaths among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region, poverty, Amerindian (Mapuche) population, typhoid fever and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, with age and sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants. Rates were highest in inland and southern regions. Compared to the northern-coast, the northern-inland region had a 10-fold risk (95% of confidence interval (95% CI): 2.4–42.2) and the southern-inland region had a 26-fold risk (95% CI: 6.0–114.2). Independent of region, other risk factors for gallbladder cancer included a high Mapuche population (Odds ratio (OR):3.9, 95% CI 1.8–8.7), high typhoid fever incidence (OR:2.9, 95% CI 1.2–6.9), high poverty (OR:5.1, 95% CI 1.6–15.9), low access to cholecystectomy (OR:3.9, 95% CI 1.5–10.1), low access to hospital care (OR:14.2, 95% CI 4.2–48.7) and high urbanization (OR:8.0, 95% CI 3.4–18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology. © 2008 Wiley-Liss, Inc.