Studies were done on the structural changes that develop in Ionescu-Shiley valves that are used as replacement heart valves for 4 to 8 years. These changes were compared with those found in similarly used porcine aortic valve (PAV) bioprostheses. A variety of morphologic differences were observed between bovine pericardial valve (BPV) and PAV bioprostheses after orthotopic implantation including: primary tissue failure associated with the use of an alignment suture, thickening of valve leaflet, leaflet tissue delamination, leaflet calcification, and dystrophic alterations of collagen. These findings indicate that valve design criteria directly influence the durability of pericardial valves. However, other factors unique to pericardial tissue also affect the durability and performance of BPVs. These factors include the inability of pericardial tissue to accommodate dynamic stresses; the extensive insudation of plasma proteins and lipids; and the inability to reduce leaflet calcification using agents that effectively mitigate calcification in PAV bioprostheses.