Abstract: Pathogenesis of nonalcoholic fatty liver (NAFLD) disease and gallbladder (GB) disease secondary to cholesterol gallstones is complex, yet both conditions share similar associated risk factors, most of them related to the metabolic syndrome. Cholecystectomy, the best treatment for GB disease, is one of the most performed abdominal surgeries worldwide. In this issue of the American Journal of Gastroenterology , Ruhl and Everhart, using data from the Third United States National Health and Nutrition Examination Survey (1988 – 1994), show that NAFLD is associated with cholecystectomy (odds ratio (OR) = 2.4; 1.8 – 3.3), but not with gallstones (OR = 1.1; 0.84 – 1.4). This fi nding suggests that cholecystectomy may itself represent a risk factor for NAFLD, which is in line with the  ecently undisclosed role of the GB and bile acids in systemic metabolic regulation. Thus, cholecystectomy may not be innocuous and may have a major impact on public health by contributing to NAFLD development.