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Recurrent embolic events are not unusual in patients with non-valvular atrial fibrillation, and management of anticoagulation in these patients can be particularly challenging. We report a case of a patient who experienced multiple embolic events in the lower extremities and cerebral circulation despite ongoing anticoagulant therapy for atrial fibrillation. The patient was an 88-year-old woman with chronic kidney disease Stage G3b who was taking oral steroids for rheumatoid arthritis. She was also taking a direct Xa inhibitor (edoxaban) for chronic atrial fibrillation, with a CHADS<sub>2</sub> score of 2 (age ≥75 years, and presence of hypertension) and a high CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 4 (2 points for age ≥75 years, 1 point for hypertension, and 1 point for female sex, for a total of 4 points). The patient had been admitted to another hospital for calculous cholangitis and experienced symptomatic improvement after stone extraction and endoscopic sphincterotomy. During treatment for cholangitis, the patient required fasting and temporary discontinuation of edoxaban for only one day. On the day after resuming the direct oral anticoagulant following a one‑day interruption, she developed acute lower limb embolic ischemia and was referred to us. The patient underwent thrombectomy for an occluded superficial femoral artery. Following the restoration of blood flow, she developed cerebral embolism perioperatively while taking a different direct Xa inhibitor (rivaroxaban). She was subsequently switched to warfarin, and no further embolism has occurred for two years. In high‑risk cases of embolism, the use of warfarin, which permits precise dose adjustment, as the anticoagulant in the relatively early postoperative period may be a reasonable consideration, although this approach remains subject to debate.