Peri‐prosthetic infection (PPI) poses a serious threat to the continued health of any patients implanted with foreign material. Tethering anti‐microbials to the surface of implanted materials for the prevention of PPI might ultimately prove to be the safest and most cost‐effective strategy. PPIs can be the result of infection by either gram‐positive bacteria (GPB) or gram‐negative bacteria (GNB), or both. Thus, broad spectrum coverage will be ultimately required. Previous work has shown the efficacy of anti‐microbial tethered surfaces. This study sought to show that antibiotics effective against both GPB and GNB could be tethered in combination to morselized bone. Vancomycin (Vanc) and tetracycline (Tet) were covalently bound to demineralized, morselized rat bone. Immunohistochemistry showed that both antibiotics were attached to allograft individually as well as in combination. To test the hypothesis that covalently attached Vanc and Tet will prevent bacterial colonization by either type of bacteria, surfaces were challenged by both S. aureus and E. coli. The antibacterial properties and efficacy were determined using confocal microscopy and colony counting. Vanc tethered bone prevented colonization by S. aureus, and Tet tethered bone prevented colonization by E. coli. A combination of both antibiotics prevented colonization by both species. These results indicate that covalent attachment of combinations of broad spectrum antibiotics to bone allograft could potentially prevent PPIs.