Prosthetic vascular graft infection remains one of the most serious complications seen after vascular surgery. Recently, fibrin glue has gained attention as a possible means to deliver drug therapies. In this study, the efficacy of vancomycin incorporated fibrin glue for preventing methicillin-resistant Staphylococcus aureus (MRSA) infection of prosthetic grafts was investigated. The vascular grafts were implanted into subcutaneous pockets in the backs of 32 rats. Group 1: no graft contamination; Group 2: MRSA contamination; Group 3: vancomycin incorporated fibrin glue graft and MRSA contamination; and Group 4: vancomycin soaked graft and MRSA contamination. The grafts were removed after 7 days and evaluated by a quantitative culture analysis. The quantitative culture values for Groups 2, 3, and 4 were 1.8x10(11) +/- 1.4x10(11), 1.1x10(7) +/- 2.4x10(7), and 2.6x10(8) +/- 3.9x10(8), respectively. The culture values of the Group 2 was significantly higher than those of the Group 3 and Group 4 (p=0.014 and p=0.016, respectively), however, Groups 3 and 4 were comparable (p=0.161). In our study, efficacies of vancomycin-incorporated fibrin and vancomycin alone were comparable. The finding of the current study indicated that a fibrin-based delivery system might not be as effective an option as a vancomycin delivery.