This study aims to determine the incremental cost of acute hospitalization for traumatic brain injury (TBI) compared with matched controls. A second purpose is to identify the factors contributing to this hospital costs.Analyses were performed on administrative data for injured patients, hospitalized in Belgium between 2009 and 2011 following a road traffic accident. Cases were matched to a control with similar injuries but without TBI. The incremental hospitalization cost of TBI and the factors contributing to the hospital costs were determined using multivariable regression modeling with gamma distribution and log link.A descriptive comparison of cases and controls shows clear differences in healthcare utilization and costs. The presence of a TBI increases the cost by a factor between 1.66 (95% confidence interval: 1.52-1.82) and 2.08 (95% confidence interval: 1.72-2.51). Regarding healthcare utilization, the most important determinants of hospital costs are surgical complexity, use of magnetic resonance imaging, intensive care unit admission, and mechanical ventilation.To our knowledge, this is the first matched-control study calculating the incremental hospitalization cost of TBI. The insights provided by this study are relevant in the context of prospective payments and can be an incentive for investments in prevention policies and extramural care.