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Study Design:Retrospective chart review. Objectives:To evaluate the efficacy of tobramycin and vancomycin powder in reducing surgical site infections in posterior lumbar instrumented fusion. Methods:A multicenter, electronic database search was conducted for all patients who underwent posterior instrumented lumbar fusions. Results:The addition of vancomycin powder decreased postoperative infections from an incidence of 5.7% down to a rate of 2.0%. This difference was statistically significant (P = .018). The addition of tobramycin powder to the wound in addition to vancomycin further decreased the infection rate down to 1.8%. The postoperative infection rate was statistically significant (P = .041) when compared with the no-powder group. However, the difference was not statistically significant (P = 1.00) when compared with vancomycin alone. There was also a trend toward gram-negative organisms with the addition of more antibiotic powder. In the control group, for example, the organisms cultured were 66% methicillin-sensitive Staphylococcus aureus and 33% gram-negative organisms. In the vancomycin group, 30% of the organisms cultured were Staphylococcus aureus and 60% gram-negative organisms. In the vancomycin and tobramycin powder group, 100% of the organisms cultured were gram-negative. Conclusions:There is a reduction in surgical site infections with addition of antibiotic powder to the wound prior to closure. However, the reduction in the infection rate was not as great with the addition of tobramycin powder to vancomycin alone and there was a noticeable change in the spectrum of organism cultured with this addition. Clinicians should consider the risk-to-benefit ratio in each case when deciding to use antibiotic powder.