Factor V Leiden mutation is commonly associated with venous thromboembolism. Although there are cases reported with prosthetic valve thrombosis, no native valve thrombosis has been reported in the literature. In this case report, we presented the concomitant aortic valve thrombosis and sinus of Valsalva aneurysm in a patient with a Factor V Leiden mutation. To the best of our knowledge, our case is the first in the literature.