Warfarin, dabigatran, and apixaban are used for preventing ischemic stroke due to non-valvular atrial fibrillation (NVAF). However, it is often challenging to select the appropriate anticoagulant. We present the case of a 70-year-old male patient with persistent NVAF who developed pulmonary thromboembolism (PTE), deep vein thrombosis (DVT), and left atrial thrombus during anticoagulant therapy with warfarin. Intravenous recombinant tissue plasminogen activator was administered during his acute PTE. Heparin and apixaban were administered over 28 days; heparin was discontinued after the DVT resolved, while apixaban was administered to prevent ischemic stroke. Two days after heparin was discontinued, the patient experienced an ischemic stroke. Dabigatran was administered for secondary ischemic stroke prevention. Soluble fibrin (SF) levels remained elevated during treatment with heparin and apixaban and returned to normal after apixaban was replaced with dabigatran. Monitoring of SF may be useful as an index for selection of anticoagulants.