Objective: To identify the cost effectiveness of vancomycin powder in the prophylaxis of posterior lumbar spine instrumentation, seeking potential savings. Methods: A retrospective, observational study was performed to evaluate the cost effectiveness. Data were retrieved from patients’ files from March 2016 to April 2017; costs were considered for the procedures, as well as which antibiotic was used. Results: A total of 184 patients were included. Of these, 102 received prophylactic treatment with 1g of cephalothin and 82 received 1g of cephalothin and 1g of vancomycin powder, which was applied to the wound prior to tissue closure. Of the 184 patients, 110 were women (59%) and 74 were men (41%), and the mean age was 55 years (24-77). The participants had a median BMI of 28.9 kg/m2 (19-39). The average cost per hospitalized patient was $3974 USD and the average cost of rehospitalization due to infection was, on average, $7700 USD. The use of vancomycin powder led to cost savings of $75,008.79 USD per 100 posterior spinal fusions performed for degenerative spine. Conclusion: The use of vancomycin powder is a cost-effective option for prophylaxis of surgical site infection in spine fusion. Level of evidence III; Economic and decision analysis.