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The Manhattan Project was a large-scale, top-secret program of the U.S. federal government created with the specific purpose of developing the world's first nuclear weapon. Each step of the manufacturing process involved potential exposures to chemical and radiological hazards for those involved. Records documenting Manhattan Project processes, activities, and individual people were not uniform, archived in various locations, and at times destroyed due to both administrative and accidental reasons, resulting in a fragmented historical record of the people and activities. Given these uncertainties, the U.S. Department of Veterans Affairs asked the National Academies to conduct a feasibility assessment to determine whether an epidemiologic study could be conducted to examine health outcomes in active-duty military veterans who participated in the Manhattan Project at 13 specified sites. The resulting report offers conclusions on the feasibility of conducting such a study and provides alternative methods to examine associations between exposures and adverse health outcomes among this population of veterans.