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The U.S. Department of Energy (DOE) established medical screening programs at the Hanford Nuclear Reservation, Oak Ridge Reservation, the Savannah River Site, and the Amchitka site starting in 1996. Workers participating in these programs have been followed to determine their vital status and mortality experience through December 31, 2004.A cohort of 8,976 former construction workers from Hanford, Savannah River, Oak Ridge, and Amchitka was followed using the National Death Index through December 31, 2004, to ascertain vital status and causes of death. Cause-specific standardized mortality ratios (SMRs) were calculated based on US death rates.Six hundred and seventy-four deaths occurred in this cohort and overall mortality was slightly less than expected (SMR = 0.93, 95% CI= 0.86—1.01), indicating a "healthy worker effect." However, significantly excess mortality was observed for all cancers (SMR = 1.28, 95% CI= 1.13-1.45), lung cancer (SMR = 1.54, 95% CI= 1.24-1.87), mesothelioma (SMR = 5.93, 95% CI =2.56-11.68), and asbestosis (SMR = 33.89, 95% CI= 18.03—57.95). Non-Hodgkin's lymphoma was in excess at Oak Ridge and multiple myeloma was in excess at Hanford. Chronic obstructive pulmonary disease (COPD) was significantly elevated among workers at the Savannah River Site (SMR = 1.92, 95% CI =1.02-3.29).DOE construction workers at these four sites were found to have significantly excess risk for combined cancer sites included in the Department of Labor' Energy Employees Occupational Illness Compensation Program (EEOCIPA). Asbestos-related cancers were significantly elevated. Am. J. Ind. Med. 52:671-682, 2009. © 2009 Wiley-Liss, Inc.