The aim of this study was to compare two variants of a novel polycarbonate polyurethane prosthesis with polyethylene terephthalate (Dacron) prosthesis in an established sheep model of carotid patch angioplasty. Two variants of the polycarbonate polyurethane prosthesis were used: (1) Polycarbonate polyurethane equal (PCU-e) prosthesis consisted of a multilayered porous structure with equal internal and external layers; (2) Polycarbonate polyurethane with more porous inner layers (PCU-mp) prosthesis had more porous inner layers than external layers. Carotid patch angioplasty was performed in 12 sheep: in six sheep, the PCU-e variant and in the other six sheep, the PCU-mp variant was implanted. Dacron patches were implanted in the contralateral carotid artery of all sheep as a control. Half of the animals with each polycarbonate polyurethane variant were euthanized after two weeks and the other half after eight weeks. Cellular infiltration, endothelialization, and neointimal hyperplasia were examined. All grafts were patent, and no thrombus was seen in any of the harvested arteries. The pores of all the three patch materials allowed infiltration of inflammatory cells, capillaries, and connective tissue. After eight weeks, a nearly complete endothelialization was visible in all patch groups without an obvious difference between the three patch materials. The neointima was thinner in the PCU patches (PCU-e: 56 ± 13 µm, PCU-mp: 119 ± 60 µm) when compared to Dacron patches (156 ± 64 µm) after two weeks. After 8 weeks, a further neointimal growth was detectable, without any significant difference of neointimal thickness between the three patch materials (Dacron: 274 ± 82 µm, PCU-e: 324 ± 98 µm, PCU-mp: 235 ± 59 µm). With the novel polycarbonate polyurethane patch materials, we achieved promising functional and morphological results with 100% patency and nearly complete endothelialization. Our findings showed at least a non-inferiority of the novel polycarbonate polyurethane patch material compared to Dacron. There were no significant differences detected between the two polycarbonate polyurethane patch variants.