With the increasing survival of heart transplant recipients, the risk for acquired allograft disease will be augmented. Severe mitral valve insufficiency after heart transplantation is rarely described. Similar to the general population, a degenerative process may affect the allograft mitral valve. Herein are reported two cases of severe mitral valve degeneration necessitating mitral valve replacement long term after heart transplantation. The pathophysiology and operative strategy for these patients are discussed.