Infection poses one of the greatest medical challenges, one further complicated by bacterial biofilm formation that renders the infection antibiotic insensitive. The goal of this investigation was to covalently link the antibiotic vancomycin (VAN) to a bone allograft so as to render the tissue inhospitable to bacterial colonization and the subsequent establishment of infection. We could achieve uniform tethering of the antibiotic to the allograft with minimal disruption of the underlying bone structure. The tethered VAN remained active against gram-positive organisms with no detectable S.aureus colonization. Additionally, the grafted VAN prevented biofilm formation, even in protected topographical niches. Attachment of the antibiotic to the allograft surface was robust-the stabilized VAN remained active for long time periods. Osteoblasts cultured on the VAN-allograft evidenced no changes in cellular phenotype. We opine that this new chimeric construct represents a superior transplantable substrate with a plethora of applications in medicine, dentistry and surgery.