Peri-prosthetic infection remains a serious complication of joint replacement surgery. Herein, we demonstrate that a vancomycin-containing sol-gel film on Ti alloy rods can successfully treat bacterial infections in an animal model. The vancomycin-containing sol-gel films exhibited predictable release kinetics, while significantly inhibiting S. aureus adhesion. When evaluated in a rat osteomyelitis model, microbiological analysis indicated that the vancomycin-containing sol-gel film caused a profound decrease in S. aureus number. Radiologically, while the control side showed extensive bone degradation, including abscesses and an extensive periosteal reaction, rods coated with the vancomycin-containing sol-gel film resulted in minimal signs of infection. mCT analysis confirmed the radiological results, while demonstrating that the vancomycin-containing sol-gel film significantly protected dense bone from resorption and minimized remodeling. These results clearly demonstrate that this novel thin sol-gel technology can be used for the targeted delivery of antibiotics for the treatment of periprosthetic as well as other bone infections. Keywords: peri-prosthetic infection; osteomyelitis; vancomycin; sol-gel; controlled release Despite the current level of operative success, bone infection remains a major complication of joint replacement surgery, especially after revision surgery. 1 This is borne out by the numbers as the infection rate after revision surgery more than triples. The most serious complication usually involves the development of a periprosthetic infection, requiring removal of the prosthesis, resection of infected soft tissue and bone, placement of an antibiotic cement spacer, prolonged period of systemic antibiotic administration with difficult recovery, and finally, reimplantation. 2,3 A major factor contributing to the development of periprosthetic infection is adherence of bacteria to the implant surface. 4,5 Upon attachment, microorganisms reorganize into specialized communities termed biofilms and produce a protective glycocalyx 6,7 that provides protection against systemic antibiotics. 8 One strategy utilized to overcome the refractivity to treatment engendered by the biofilm is to administer high doses of antibiotics at the bone-implant interface. 2 However, due to the uncontrolled and rapid release of the antibiotic at the target site many of the delivery systems have proved to be of limited value. Moreover, the carrier itself can serve as a nidus for further microbial colonization. [9][10][11] Release from a room temperature processed sol-gel film provides a novel mechanism for the controlled local delivery of drugs or antibiotics. Silica sol-gel based glass has been shown to be an effective carrier for transforming growth factor b1, 12 trypsin inhibitor, 13 vancomycin, 14 and other molecules. 15 Furthermore, because porosity as well as pore size can be varied, predictable and controlled elution kinetics can be generated. We have chosen to test the efficacy of an antibiotic-containi...