A spectrum of events leading to tissue failure is responsible for late dysfunction of Hancock porcine valve xenografts: (a) Primary failure: dystrophic calcification, thrombosis, fibrous tissue overgrowth, primary tears, cuspal hematomas, and stent postbending. (b) Secondary failure: endocarditis and paravalvular leak. Dystrophic calcification is the main factor influencing long-term durability and accounts in our experience for 88% of primary failure, through different clinical presentations; particularly, incompetence by cusp tearing and egg-shell fragmentation is by far the most frequent mode of failure. Cusp degeneration by primary tears (in the absence of dystrophic calcification) is an uncommon event, due to lipid infiltration or to right coronary muscle shelf spontaneous or immuno-related disruption.