The goal of this research was to evaluate the in vitro stability of fibrin coatings on polymeric materials in the presence of plasmin. Factor XIIIa-crosslinked and noncrosslinked fibrin layers were coated on three different polyurethane substrates: Corethane™, Tegaderm, and a biodegradable polyurethane, PCL/HDI/Phe. Degradation assays indicated that crosslinking the fibrin coatings enhanced the stability of the coatings on both Tegaderm and PCL/HDI/ Phe; however, the persistence of the coating on the woven Corethane™ was not influenced by crosslinking. Degradation assay results also showed that the fibrin coating on the Corethane™ was significantly less stable than the fibrin coatings on the Tegaderm and PCL/HDI/Phe films. The chromogenic substrate assay data showed crosslinking did not affect the specific plasmin activity on the coatings; therefore, the increased stability resulting from crosslinking was not achieved through a reduction of fibrinolysis. The plasmin activity on the coated Corethane™ samples was much greater than that on either of the coated flat wound dressing materials. The large surface area of Corethane™, a porous woven vascular graft material, may have had a direct influence on the fibrinolysis of its coatings by providing a large number of tissue-type plasminogen activator (tPA) binding sites. A thin, crosslinked, fibrin-coated polyurethane provides a theoretically attractive biomaterial for use in a wound dressing application and should be subject to ongoing research.