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Traumatic brain injury (TBI) is the leading cause of death from blunt trauma, with an estimated cost to society of over $40 billion annually. Evidence-based guidelines for TBI care have been widely discussed, but in-hospital treatment of these patients has been highly variable. The purpose of this study was to determine whether management of TBI patients according to a protocol based on the Brain Trauma Foundation (BTF) guidelines would reduce mortality, length of stay, charges, and disability.In 1995, a protocol following the BTF guidelines was developed by members of the Level I trauma center’s interdisciplinary neurotrauma task force. Inclusion criteria for the protocol were blunt head injury, age > 14 years, and Glasgow Coma Scale score ≤ 8. An extensive educational process was conducted to develop compliance among all disciplines for this new management strategy. A historical control group of patients eligible for the protocol was identified by retrospective analysis of trauma registry data for 1991 to 1994. Mortality, intensive care unit days, total hospital days, total charges, Rancho Los Amigos Scores, and Glasgow Outcome Scale scores were compared.Between 1991 and 2000, over 7,000 blunt TBI patients were managed by the Trauma Service. Of these, 830 met the inclusion criteria for the TBI protocol and lived > 48 hours. After implementation, initial analysis of the 1995–96 cohort indicated only 50% compliance with the protocol. By 1997, compliance had risen to 88%. Patients were therefore compared as three groups: before the protocol (1991–94, n = 219), during low compliance (1995–96, n = 188), and during high compliance (1997–2000, n = 423). Groups did not differ significantly on Injury Severity Score, head Abbreviated Injury Scale score, or age (p > 0.05). Admission Glasgow Coma Scale score was slightly higher in the 1991–94 cohort (4.0 vs. 3.5, p = 0.001). From 1991–94 to 1997–2000, intensive care unit stay was reduced by 1.8 days (p = 0.021) and total hospital stay was reduced by 5.4 days (p < 0.001). The charge reduction (calculated in 1997 dollars) per patient for the length of stay decrease was $6,577 in 1995–96 and $8,266 in 1997–2000 (p = 0.002). This represents a total reduction over 6 years of $4.7 million in charges. In addition, the overall mortality rate showed a reduction of 4.0% from 1991–94 to 1997–2000 (17.8% vs. 13.8%), although this was not statistically significant. On the basis of the Glasgow Outcome Scale score, in 1997–2000, 61.5% of the patients had either a “good recovery” or only “moderate disability,” compared with 50.3% in 1995–96 and 43.3% in 1991–94 (p < 0.001). The Rancho Los Amigos Scores showed a similar trend, with 56.6% of the 1997–2000 patients having appropriate responses at 10 to 14 days, compared with only 44.0% of the 1995–96 patients and 43.9% of the 1991–94 patients (p = 0.004).Adherence to a protocol based on the BTF guidelines can result in a significant decrease in hospital days and charges for TBI patients who live > 48 hours. In addition, mortality and outcome may be significantly affected. This analysis suggests that increased efforts to improve adherence to national guidelines may have a significant impact on head injury care outcomes and could dramatically reduce the substantial financial resources that are currently consumed in the acute care phases for this injury.