This study investigated the in vivo hemodynamics and pathologic changes of a unileaflet pericardial bioprosthetic valve 3 to 5 months after implantation in juvenile sheep. Group 1 had 10 sheep with tricuspid valve replacement. Group 2 had nine sheep with mitral valve replacement. Group 3 served as a control with 10 sheep that had tricuspid valve replacement with a trileaflet porcine bioprosthesis. Hemodynamic performance was satisfactory in all three groups despite prominent pathologic changes, particularly in unileaflet valves. Intrinsic cuspal calcification was present in 66% of the unileaflet tricuspid, 88% unileaflet mitral, and 25% porcine tricuspid valves. Neither cuspal tearing nor perforations were found. However, cuspal stretching and redundancy of the mobile cusp was present in six tricuspid, seven mitral unileaflet valves, and no porcine valves. Gross pericardial redundancy correlated with the microscopic appearance of distorted and separated collagen bundles. These findings suggest that multiple modes of primary tissue failure may limit the durability of this unileaflet pericardial valve.