['Retrospective comparative study using prospectively collected data.', 'To compare the rate of infection with and without the use of vancomycin powder application during posterior cervical instrumentation.', 'Surgical site infections (SSI) are a significant source of morbidity in multilevel posterior-instrumented fusions for cervical spondylotic myelopathy (CSM). Local delivery of antibiotics has been associated with decreased rates of SSI in posterior-instrumented fusions, but no study has addressed the effects of these measures on a population composed of exclusively multilevel posterior cervical instrumentation performed with decompression for CSM.', 'All patients undergoing multilevel posterior decompression and instrumentation for CSM by a single surgeon from 2003-2011 were included. Post hoc analysis of prospectively collected data was analyzed comparing consecutive patients treated without the use of vancomycin powder with those treated after the initiation of vancomycin powder prophylaxis. Intervention cohort and controls were examined for differences in SSI rate, body mass index, neurological status, comorbidities, and complications.', 'A total of 112 patients were included in the study. Intervention (n = 40) and control (n = 72) groups were statistically similar with regard to age, body mass index, comorbidities, estimated blood loss, and operative time. Univariate analysis showed a significant decrease in infection rate in the intervention group (0%) compared with the control group (15%) in this high-risk population (P = 0.007; power = 81%). No adverse events were noted in the intervention group associated with the use of vancomycin powder.'] Does intrawound vancomycin powder reduce surgical site infections in posterior cervical fusion?