Objective: To determine the incidence of liver disease with UPA versus gonadotropin-releasing hormone (GnRH) agonists using Korea's national health claim data. Methods: This study is a retrospective nationwide cohort study using Korean national health claim data from 2010 to 2018. Women with a diagnosis of uterine fibroids were divided into two treatment groups: the UPA and GnRH agonist groups. Severe liver disease, mild liver disease, and liver transplantation were confirmed according to the diagnostic code or surgical code. Results: Among the patients with uterine fibroids,17,207 patients were treated with GnRH agonists and 20,926 patients with UPA. After 1:1 propensity score matching for each group, there were 11,445 individuals. Neither group had a liver transplantation case. In the conditional logistic regression analysis, the incidences of total liver diseases (odds ratio [OR] 1.111, 95% confidence interval [CI] 1.015-1.216) and mild liver diseases (OR 1.103, 95% CI 1-1.217) were higher in the UPA group than in the GnRH agonist group, but those of severe liver diseases (OR 0.07, 95% CI 0.001-4.417) and toxic liver disease (OR 1.258, 95% CI 0.844-1.875) did not differ between the groups. Conclusion: The incidences of severe liver disease, hepatic failure, and toxic liver disease were not different between the UPA and GnRH agonist groups. However, the incidence of mild liver disease was higher in the UPA group than in the GnRH agonist group. The incidence of hepatic damage with UPA was very low.