Objectives: The prevalence of atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) is high and increasing, however, evidence is insufficient and conflicting regarding oral anticoagulant (OAC) use in these patients. Methods: This retrospective cohort study included patients in the Korea National Health Insurance System diagnosed with AF after ESKD onset from January 2007 to December 2017. The primary outcome was all-cause death. Secondary outcomes were ischemic stroke, hospitalization for major bleeding, and major adverse cardiovascular event (MACE). Outcomes were compared between OAC users group and nonusers using 6-month landmark analysis and 1: 3 propensity score matching. Results: Among patients with ESKD and AF, the number of prescribed OACs increased 2.3-fold from 2012 (n=3,579) to 2018 (n=8,341) and the proportion prescribed direct OACs increased steadily from 2012 (0%) to 2018 (51.4%). After propensity score matching, OAC users had lower risk of all-cause death (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55–0.81), ischemic stroke (HR 0.61, 95% CI 0.41–0.89), and MACE (HR 0.70, 95% CI 0.55–0.90) no increased risk of hospitalization for major bleeding (HR 0.99, 95% CI 0.72–1.35), compared to OAC nonusers. Unlike warfarin, direct OACs were associated with a reduced risk of all-cause death and hospitalization of major bleeding. Conclusions: In patients with ESKD and AF, OACs were associated with reduced all-cause death, ischemic stroke, and MACE.