Background: Expanded polytetrafluoroethylene (ePTFE), an ideal bioimplant material, is commonly used in surgical repair to treat soft tissue defects and deformities. However, the main disadvantage of ePTFE is that its distinctive porous ultrastructure is prone to bacterial adhesion that gives rise to infection and chronic inflammation, resulting in functional failure. Herein, a potentially promising approach to ePTFE autologous vascularization (AV-ePTFE) in vivo was established and developed to enhance the material's antibacterial properties. Methods: Hematoxylin and eosin (H&E) staining and visual observation were performed to validate the intensity of the inflammatory response and related histological changes in surgical wounds after AV-ePTFE implantation. In addition, the antibacterial activities of AV-ePTFE were assessed by an in vitro bacterial adhesion assay and scanning electron microscope observation. Results: The optimal time point of AV-ePTFE was 12 weeks after implantation. AV-ePTFE relieved inflammation based on an inflammation grading evaluation and expedited wound healing. Furthermore, AV-ePTFE effectively reduced the number of bacterial adhesions, inhibited bacterial biofilm formation, and prevented the occurrence of infection. Conclusions: We conclude that autologous vascularization is an effective method to improve the antibacterial adhesion properties and biocompatibility of ePTFE after implantation and that it may have a significant effect on clinical application of future porous biomaterials.