The present case first describes the spontaneous thigh hematoma induced by enoxaparin in a hemodialysis patient. A 64-year-old woman on a hemodialysis therapy was diagnosed with acute coronary syndrome, and treated with enoxaparin. Ten days after enoxaparin administration, diffuse swelling and pain developed suddenly in the right thigh without a history of trauma. There was a weak arterial pulse below the knee with an abrupt decrease of hemoglobin level. There were no significant abnormalities in the coagulation tests including the platelet count, prothrombin time, and activated partial thromboplastin time. Computed tomographic (CT) angiography and lower extremity arteriography were performed, which showed several bleeding foci involving branches of the right deep femoral artery. She was treated successfully by embolization at the bleeding sites, along with a transfusion.