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The National Study on the Costs and Outcomes of Trauma Care (NSCOT) was designed to address the need for better information on the value of trauma center care. It is a multi-institutional, prospective study that involved the examination of costs and outcomes of care received by over 5,000 adult trauma patients 18 to 84 years of age treated at 69 hospitals located in 12 states. The study had three major objectives: (1) to examine variations in care provided to trauma patients in Level I trauma centers and nontrauma center hospitals; (2) to determine the extent to which differences in care correlate with patient outcome, where outcome is defined not just in terms of mortality and morbidity, but also in terms of major functional outcomes at 3 months and 12 months after injury; and (3) to estimate acute and 1-year treatment costs for trauma center and nontrauma center care, and to describe the relationship between costs and effectiveness for trauma centers and nontrauma centers. In this article, we describe the design of the NSCOT study and point to some of the methodological challenges faced in its implementation and in the analysis of the data. We also present a description of the study population to serve as a basis of future reports. We conclude with lessons learned and some recommendations for future research.