Background:This study aimed to evaluate the characteristics and clinical outcomes (major bleeding [MB] and thromboembolic events [TEEs]) of atrial fibrillation (AF) patients with chronic kidney disease (CKD)who receiveddirect oral anticoagulant (DOAC) therapy. Methods:Data prospectivelycollected from a single-center registry containing 2,272 patients with DOAC prescription for AF (apixaban [n=1,014], edoxaban [n=267], rivaroxaban [n=498], and dabigatran[n=493]) were retrospectively analyzed. Patients were monitored for two years and classified into the CKD (n=1460) andnon-CKD groups(n=812). MB and TEEs were evaluated. Results:The mean age was 72±10 years, with the CHADS2,CHA2DS2-VASc, and HAS-BLED scores being 1.95±1.32, 3.21±1.67, and 1.89±0.96,respectively.Incidence rates of MB and TEEs were 2.3%/year and 2.1%/year, respectively. The CKD groupwasolderand had lower body weight and higher CHADS2,CHA2DS2-VASc, and HAS-BLED scoresthanthe non-CKD group.Kaplan–Meier curve analysis revealed that the incidence of MB and TEEs was higher in the CKD group. Multiple logistic regression analysis in the CKD group revealed thatage andstroke history were independent determinants of TEEs, and low body weighttended to be a determinant of MB.The inappropriate low dose use was higher for apixaban than other DOACs in the CKD group. Consequently, for apixaban, the incidence of stroke was significantly higherin the CKD group than in the non-CKD group. Conclusion:Patients with CKDwere characterized by factors that predisposed them to MB and TEEs, such as older age and low body weight. In a single-center registry, only treatment with apixaban in the CKD group led to a higher incidence of TEEs.