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To compare the effectiveness of both vancomycin powder and antibiotic bead placement to irrigation and debridement alone in prevention of infection in a contaminated open fracture model in rats.In a previously described model of contaminated open fractures, 45 rats had simulated open fractures created, stabilized, and contaminated with Staphylococcus aureus. They were then treated 6 hours later with 3 interventions: irrigation and debridement alone (control group) or in combination with placement of polymethyl methacrylate beads containing vancomycin and tobramycin powders (antibiotic bead group) or placement of 10 mg of intrawound vancomycin powder (powder group). Rats were allowed to recover and then killed 14 days later for harvest of femurs and plates. Femurs and plates were both incubated overnight, and bacterial colonies were counted in each group for comparison.Quantitative counts of bacteria in bone showed significantly reduced growth in both bead and powder groups when compared with control group (P < 0.0001). Quantitative counts of bacteria in plates showed significantly reduced growth in both bead and powder groups when compared with control group (P < 0.0003; 0.029). No significant differences were seen in bacterial growth between bead and powder groups for either bones (P = 0.13) or plates (P = 0.065).When compared with irrigation and debridement alone, placement of intrawound vancomycin powder significantly decreased bacterial load in a contaminated open fracture model in rats similar to placing antibiotic beads. This may provide an additional adjuvant treatment that does not require a secondary surgery for bead removal.