Background: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen.Objective: We derived a meta-exposure–response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios.Methods: We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE.Results: We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure.Conclusions: Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively.Citation: Vermeulen R, Silverman DT, Garshick E, Vlaanderen J, Portengen L, Steenland K. 2014. Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts. Environ Health Perspect 122:172–177; http://dx.doi.org/10.1289/ehp.1306880