Supplemental Digital Content is available in the text Using hospital discharge and microbiology data from 129 U.S. hospitals, the authors found that Staphylococcus aureus infections post elective posterior instrumented spinal fusion surgeries are associated with significantly higher hospitalization cost, length of stay, and 180-day risk of readmission compared with those with no such infection. Study Design.: A retrospective cohort study. Objective.: The aim of this study was to assess hospital resource utilization and costs associated with Staphylococcus aureus infection within 180 days post elective posterior instrumented spinal fusion surgeries (index surgery) between 2010 and 2015. Summary of Background Data.: Surgical site infections (SSIs) and blood stream infections (BSIs) post spinal fusion surgeries are associated with worse clinical outcomes and increased costs. Economic data specific to the most common pathogen of infections post spinal fusion surgeries, S. aureus, are limited. Methods.: We analyzed hospital discharge and microbiology data from 129 U.S. hospitals in Premier Healthcare Database. Selection criteria included age ≥ 18 years; had a primary/secondary ICD-9-CM procedure code for index surgery; and had microbiology data during study period. Outcomes included total hospitalization cost, length of stay, and risk of all-cause readmission. Infection status was classified as culture-confirmed invasive (i.e. , BSIs, deep or organ/space SSIs), any, and no S. aureus infection. Multivariable regression analyses were used to compare outcome variables between infection groups controlling for known confounders. Results.: Two hundred ninety-four patients had any S. aureus infection (151 had invasive infection) and 12,918 had no infection. Compared with no infection group, invasive and any infection groups had higher total hospitalization cost (adjusted mean in 2015 U.S. dollars: $88,353 and $64,356 vs. $47,366, P < 0.001), longer length of stay (adjusted mean: 20.98 and 13.15 vs. 6.77 days, P < 0.001), and higher risk of all-cause readmission [adjusted risk ratio: 2.15 (95% confidence interval: 2.06–2.25) for invasive and 1.70 (95% confidence interval: 1.61–1.80) for any infection groups]. Conclusion.: S. aureus infections post elective posterior instrumented spinal fusion surgeries are associated with significantly higher hospitalization cost, length of stay, and 180-day risk of readmission than those with no such infection, which presents substantial burden to hospitals and patients. Reducing such infections may cut costs and hospital resource utilization. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]