Intravenous recombinant tissue plasminogen activator is not recommended for the treatment of acute ischemic stroke in patients with infective endocarditis due to the risk of hemorrhagic transformation of septic emboli and few reported cases in the literature. Here, we present the successful outcome of intravenous recombinant tissue plasminogen activator administration for a patient with acute ischemic stroke who was later found to have infective endocarditis. This case adds to the small number of cases reported in the literature.