There is still a lack of knowledge on the association between cholecystectomy and liver disease. This systematic review and meta-analysis was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy.PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model.We identified 20 studies with a total of 27,320,709 individuals and 283,633 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR 1.63, 95% CI 1.34-1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR 1.54, 95% CI 1.18-2.01), a 173% increased risk of cirrhosis (OR 2.73, 95% CI 1.81-4.12), and a 46% increased risk of primary liver cancer (OR 1.46, 95% CI 1.18-1.82).There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.