This study was undertaken to assess the utility of a swine model for evaluation of the thrombotic potential of mechanical prosthetic valves. Twenty-two swine underwent mitral valve replacement using three different bileaflet mechanical valve designs. Animals were placed in one of three anticoagulation protocols (group I, INR of 3.0-3.5; group II, INR of 2.0-2.5; group III, no anticoagulation) and followed for 20 weeks. Twenty-one animals survived the immediate postoperative period. Ten of 13 animals receiving anticoagulation died from hemorrhagic complications (hemopericardium) within the first 30 postoperative days. Eight of nine animals not receiving anticoagulation survived for long-term evaluation. All valves from long-term survivors showed marked fibrous sheathing. Perivalvular defects and organized thrombi were also seen in valves explanted from long-term survivors. Difficulty in maintaining safe levels of anticoagulation (resulting in a high incidence of hemorrhagic complications), marked fibrous sheathing and associated thrombosis, and a high incidence of perivalvular defects were significant factors limiting the utility of this model.