Prosthetic valve endocarditis(PVE)occasionally evokes sepsis and disseminated intravascular coagulation(DIC). A 46-year-old man developed relapsing active PVE with an annular abscess and suffered from exacerbating sepsis and DIC. Despite the administration of antibiotics, his DIC score increased. Anti-DIC treatment with recombinant thrombomodulin (rTM) was initiated, and his DIC was remarkably resolved. Accordingly, the abscess cavity was closed by using a homograft anterior mitral leaflet, and the aortic root was replaced with the homograft. He is doing well without an evidence of recurrent endocarditis 18 months after the operation. rTM is a new and promising drug for the treatment of DIC with infective endocarditis.