Rationale: Previous studies have shown associations between dust exposure or lung burden and emphysema in coal miners, although the separate contributions of various predictors have not been clearly demonstrated. Objectives: To quantitatively evaluate the relationship between cumulative exposure to respirable coal mine dust, cigarette smoking, and other factors on emphysema severity. Methods: The study group included 722 autopsied U.S. coal miners and non-miners. Data on work history, smoking, race, and age at death were obtained from medical records and questionnaire completed by next-of-kin. Emphysema was classified and graded using a standardized schema. Job-specific mean concentrations of respirable coal mine dust were matched with work histories to estimate cumulative exposure. Relationships between various metrics of dust exposure (including cumulative exposure and lung dust burden) and emphysema severity were investigated in weighted least squares regression models. Measurements and Main Results: Emphysema severity was significantly elevated in coal miners compared to non-miners, among both ever and never smokers (p<0.0001). Cumulative exposure to respirable coal mine dust or coal dust retained in the lungs were each significant predictors of emphysema severity (p<0.0001), after accounting for cigarette smoking, age at death, and race. The contributions of coal mine dust exposure and cigarette smoking were similar in predicting emphysema severity averaged over this cohort. Conclusions: Coal dust exposure, cigarette smoking, age, and race are significant and additive predictors of emphysema severity in this study.