BACKGROUND: Surgical site infections can complicate posterior spine surgery. Multiple hospital admissions may be required to adequately treat a surgical site infection, which is associated with increased costs and lower patient satisfaction. The objective of this study was to evaluate the efficacy of prophylactic intra-wound vancomycin powder in reducing the incidence of repeat surgery for infections after posterior instrumented and noninstrumented spine surgery. METHODS: A series of consecutive patients who underwent instrumented or noninstrumented posterior spine surgery for any indication by two surgeons from July 2010 to July 2012 were reviewed. The preoperative antibiotic regimens of both surgeons were identical, except that one surgeon applied 1 g vancomycin powder directly to the surgical bed before wound closure, while the other did not. Patient demographics, operative details, and rates of reoperation for wound infection in the control and the treatment groups were compared. RESULTS: Both the control group and treatment group consisted of 150 patients; mean ages were 58.33 and 54.14 years, respectively. Both groups had low rates of deep infection requiring surgical intervention. The treatment group had a significantly lower rate of infection requiring reoperation or surgical debridement (0 %; 95 % CI: 0 %-2.4 %) compared with the control group (4 %; 95 % CI: 1.5 %-8.5 %) (P = 0.0297). The six infections identified in the control group resulted in 12 repeat operative debridement procedures. Gram-positive organisms were identified in 66.7 % of infections. No complications were related to the application of vancomycin powder. CONCLUSIONS: The results of this study demonstrate that adjunctive vancomycin powder applied directly to the surgical bed before closure seems effective in preventing deep infections that require operative debridement following posterior spine surgery.