30 patients undergoing total knee arthroplasty were randomized to one of three groups for antibiotic prophylaxis: 1g intravenous (IV) vancomycin, 250mg intraosseous regional administration (IORA) vancomycin, and 500mg IORA vancomycin. Subcutaneous fat and femoral bone samples were collected throughout the procedure and assessed for antibiotic concentration. The results demonstrated significantly higher concentrations of vancomycin in tissue samples in the two intraosseous vancomycin groups (both 250mg and 500mg) when compared to the 1g IV vancomycin group.