Abstract Background Data about the use of direct oral anticoagulants (DOACs) in the prospective registry of Asian atrial fibrillation (AF) patients with renal dysfunction, especially those with a creatinine clearance (CCr) between 15 to 30 ml/min, are limited. This study aimed to investigate the safety of rivaroxaban in Taiwanese AF patients with renal impairment in the daily practice. Methods XARETO (Xarelto for the prevention of stroke and non-central nervous systemic embolism in non-valvular atrial fibrillation with REnal impairment in Taiwanese pOpulation) is a multi-center, non-interventional, single arm prospective observational cohort study performed in Taiwan. Subjects with non-valvular AF aged >=20 years with a documented CCr of 15-50 ml/min within 6 months before the enrollment were enrolled. All subjects were prescribed rivaroxaban for stroke prevention. The major bleeding was defined as a bleeding events with fall in Hgb of >=2 g/dL or a transfusion of >= 2 units of packed red blood cells or whole blood or occurrence of bleeding at a critical site or mortality. Results A total of 493 patients were enrolled. The mean age was 78.3 years old and 59.6% was male. The mean CHA2DS2-VASc and HAS-BLED scores were 4.4 and 2.9, respectively. Co-morbidities were as follows: 41.0% patients had chronic heart failure, 83.2% had hypertension, 40.8% had diabetes and 14.8% had prior stroke/transient ischemic attack/systemic embolic events. The mean CCr was 35.19 ml/min, and 159 (32.3%) of them has a CCr between 15-29 ml/min. During the follow up, there were 23 patients with 26 adjudicated major bleeding events with the incidence rate of 6.2 per 100 person-years (95% CI 3.9-9.3). Of these patients, there were 15 patients with 16 adjudicated major bleeding events considered as related to the rivaroxaban treatment with the incidence rate of 4.0 per 100 person-years (95% CI 2.2-6.6)(Figure) Conclusions In high-risk Taiwan AF patients (mean CHA2DS2-VASc score 4.4) with renal impairment (mean CCr 35.19 ml/min, 32.3% between 15-29 ml/min), the safety of rivaroxaban was confirmed in the prospective XARETO study.