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In total, 496 patients of a single surgeon cohort examining the surgical-site infection (SSI) rates with the addition of vancomycin powder in both diabetic and revision spine surgery cases. A historical control group of 652 patients were compared from the same surgeon over an earlier time period before the inception of using vancomycin powder prophylaxis.The objective of this study was to describe and compare the rates of infection in high-risk patient populations while using vancomycin powder.Vancomycin powder may not decrease an already low rate of infection. Therefore, use of vancomycin powder in high-risk patients with a higher rate of infection would potentially show benefit of vancomycin powder.In total, 496 patient charts were collected from a database of cases. Patients were included in the cohort if they had revision spinal operation or if they were diabetic. Patients in the time period July 2010 to August 2013 were included in the vancomycin protocol where 1 g of vancomycin powder was added to the wound before wound closure. Cases were considered positive if there was a positive culture or if there was sufficient clinical suspicion to treat. As a control to this cohort, 692 charts were reviewed from a earlier time period of the same surgeon and institution.In total, 28 patients of 496 (5.6%) patients in the cohort returned to the operating room for seroma, hematoma, draining wound, or infection. Sixteen of these patients (16/496, 3.2%) had a culture positive infection or were treated as an infection. This rate was significantly lower than the historical rate before the protocol.Although vancomycin does seem to be useful in decreasing SSIs, it is not a panacea. SSIs in high-risk patients were not completely eliminated by the vancomycin protocol.