Prosthetic valve endocarditis is a relatively rare condition associated with high mortality. Endocarditis affecting 2 successive mechanical valves at the aortic position has not, to the best of our knowledge, been described. We reported such a patient whose condition was further complicated by mitral regurgitation, pulmonary hypertension, worsening heart failure, and cardiac conduction abnormalities. Considering the failure of 2 previous mechanical valves, we conducted a homograft replacement of the aortic root with coronary reattachment. Mitral regurgitation was treated by annuloplasty. The patient's early postoperative course was uneventful and he was doing well 16 months after surgery. We discuss the overall treatment strategy for recurrent prosthetic valve endocarditis and potential homograft advantages.