The clinical implementation of percutaneous implants is still limited owing to infections at the side of the stoma. In our concept, this issue is addressed by designing copolymer surface coatings possessing biocompatibility and antimicrobial activity to improve the maintenance of a physiological skin seal at the skin-implant interface. Different copolymers with surface-active phosphonate and antimicrobial cationic groups were designed. Thus, coated titanium samples were cultured with bacterial strains or fibroblasts, respectively. Antimicrobial impact was evaluated by imaging the reduction of bacterial adherence. Biocompatibility was displayed by fibroblast proliferation and morphology. A variety of copolymers of 4-vinylpyridine with vinylbenzylphosphonate or dimethyl(2-methacryloyloxy-ethyl) phosphonate were prepared by free radical polymerization. The optimized polymer coating (copolymer D) showed a reduction of adherent bacteria up to 95%, with only a slight reduction in the adherence of human fibroblasts compared with blank titanium controls. In this study, we demonstrate in vitro that polymer surface coatings can be simultaneously antimicrobial and biocompatible. We consider this to be a promising technology for the realization of a permanent aseptic percutaneous passage as needed for the advancement of osseointegrated limb prosthesis.