Transfemoral aortic valve implantation has become an important interventional technique for patients with severe aortic stenosis and high surgical risks. The mitral valve has been a much greater challenge for interventional procedures, and no percutaneous mitral valve implantation system has yet been developed and approved. Here, we report the successful transfemoral, antegrade, valve-in-valve implantation of the SAPIEN XT valve (Edwards Lifesciences) into a degenerated mitral valve bioprosthesis. The patient was an 81-year-old woman with severe regurgitation of her 27 mm Epic mitral valve prosthesis (St. Jude Medical), suffering from dyspnea on mild exertion with a calculated logistic EuroScore of 48% and an Society of Thoracic Surgeons score of 29%. Thus, another surgical mitral valve replacement was refused by the patient and was considered as extremely high risk by the cardiac surgeon. Therefore, a transfemoral valve-in-valve implantation was planned. The femoral vein was used as an access site, followed by a transseptal puncture and placement of a super-stiff wire into the left ventricle. Then, the septum was dilated and a 26 mm SAPIEN XT valve was inserted through the septum and then inserted into the mitral valve prosthesis. Under rapid pacing, a very slow inflation of the balloon was performed, leading to a stable valve-in-valve implantation without any regurgitation. The patient was transferred to a normal ward after 2 days. This procedure is an off-label, technically very challenging, high-risk implantation that could be attempted in very select patients after discussion by a heart team and by experienced implanters.