OBJECTIVES: Adherence to pediatric traumatic brain injury guidelines has been associated with improved survival and better functional outcome. However, the relationship between guideline adherence and hospitalization costs has not been examined. To evaluate the relationship between adherence to pediatric severe traumatic brain injury guidelines, measured by acute care clinical indicators, and the total costs of hospitalization associated with severe traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: Five regional pediatric trauma centers affiliated with academic medical centers. PATIENTS: Demographic, injury, treatment, and charge data were included for pediatric patients (17 yr) with severe traumatic brain injury. INTERVENTIONS: Percent adherence to clinical indicators was determined for each patient. Cost-to-charge ratios were used to estimate ICU and total hospital costs for each patient. Generalized linear models evaluated the association between healthcare costs and adherence rate. MEASUREMENTS AND MAIN RESULTS: Cost data for 235 patients were examined. Estimated mean adjusted hospital costs were $103,485 (95% CI, 98,553-108,416); adjusted ICU costs were $82,071 (95% CI, 78,559-85,582). No association was found between adherence to guidelines and total hospital or ICU costs, after adjusting for patient and injury characteristics. Adjusted regression model results provided cost ratio equal to 1.01 for hospital and ICU costs (95% CI, 0.99-1.03 and 0.99-1.02, respectively). CONCLUSIONS: Adherence to severe pediatric traumatic brain injury guidelines at these five leading pediatric trauma centers was not associated with increased hospitalization and ICU costs. Therefore, cost should not be a factor as institutions and providers strive to provide evidence-based guideline driven care of children with severe traumatic brain injury.