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The cost of trauma center care is high, raising questions about the value of a regionalized approach to trauma care. To address these concerns, we estimate 1-year and lifetime treatment costs and measure the cost-effectiveness of treatment at a Level I trauma center (TC) compared with a nontrauma center hospital (NTC).Estimates of cost-effectiveness were derived using data on 5,043 major trauma patients enrolled in the National Study on Costs and Outcomes of Trauma, a prospective cohort study of severely injured adult patients cared for in 69 hospitals in 14 states. Data on costs were derived from multiple sources including claims data from the Centers for Medicare and Medicaid Services, UB92 hospital bills, and patient interviews. Cost-effectiveness was estimated as the ratio of the difference in costs (for treatment at a TC vs. NTC) divided by the difference in life years gained (and lives saved). We also measured cost-effectiveness per quality-adjusted life year gained where quality of life was measured using the SF-6D. We used inverse probability of treatment weighting to adjust for observable differences between patients treated at TCs and NTCs.The added cost for treatment at a TC versus NTC was $36,319 per life-year gained ($790,931 per life saved) and $36,961 per quality-adjusted life years gained. Cost-effectiveness was more favorable for patients with injuries of higher versus lower severity and for younger versus older patients.Our findings provide evidence that regionalization of trauma care is not only effective but also it is cost-effective.