Purpose This study investigates health disparities for adults residing in a mountaintop coal mining area of Appalachian Kentucky. Mountaintop mining areas are characterized by severe economic disadvantage and by mining‐related environmental hazards. Methods A community‐based participatory research study was implemented to collect information from residents on health conditions and symptoms for themselves and other household members in a rural mountaintop mining area compared to a rural nonmining area of eastern Kentucky. A door‐to‐door health interview collected data from 952 adults. Data were analyzed using prevalence rate ratio models. Findings Adjusting for covariates, significantly poorer health conditions were observed in the mountaintop mining community on: self‐rated health status, illness symptoms across multiple organ systems, lifetime and current asthma, chronic obstructive pulmonary disease, and hypertension. Respondents in mountaintop mining communities were also significantly more likely to report that household members had experienced serious illness, or had died from cancer in the past 5 years. Significant differences were not observed for self‐reported cancer, angina, or stroke, although differences in cardiovascular symptoms and household cancer were reported. Conclusions Efforts to reduce longstanding health problems in Appalachia must focus on mountaintop mining portions of the region, and should seek to eliminate socioeconomic and environmental disparities.