A 62-year-old female with Osler's disease was admitted to our hospital because of fever and cardiac failure. The patient had undergone a mitral valve replacement (MVR) using a Carpentier-Edwards prosthetic valve 14 years earlier. A bacterial examination of arterial blood identified Streptococcus mitis. No arteriovenous malformations were detected in visceral organs. The patient underwent MVR using the same prosthetic xenograft after conservative treatment and management of repetitive epistaxis and decayed teeth. Intra- and postoperative bleeding were typical of a mitral valve reoperation. This is the first reported experience, to the best of our knowledge, of a second MVR in a patient with Osler's disease.