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Edoxaban is an oral anticoagulant drug that directly inhibits factor Xa. It is used for stroke prophylaxis, venous thromboembolism prophylaxis / treatment, and secondary prophylaxis of acute coronary syndromes. Drug interactions with edoxaban are rare and there is no need for routine blood monitoring. Clinicians should be more aware of potential complications and complication management, as they are prescribed quite frequently. In this article, a spontaneous renal hematoma in a patient using edoxaban for atrial fibrillation-induced stroke prophylaxis is reported. The treatment and follow-up decisions were made by the multidisciplinary team and the patient died despite all efforts. The use of these drugs should be carefully questioned in patients with bleeding who apply to the emergency room because they do not change the coagulation parameters. Larger case series and case reports are needed to develop treatment algorithms for fatal complications that may occur during their use.