This study investigates associations between measures of socioeconomic condition and rates of premature mortality for leading causes of death for counties in the U.S., with a focus on the Appalachian region. The overall goal is to elucidate relationships between observed health outcomes in the region and underlying socioeconomic conditions that may be contributing factors in shaping these outcomes. The motivation for this investigation arose from findings in an earlier study conducted for the Appalachian Regional Commission entitled An Analysis of Disparities in Health Status and Access to Medical Care in the Appalachian Region (Halverson et al, 2004) which found that the “Appalachia continues to suffer adverse socio-economic conditions (higher unemployment, lower educational achievement, lower per capita income), and there does appear to be some association between areas with more adverse socioeconomic conditions and adverse health outcomes.” Yet, the report noted that “…the direct role of socioeconomic conditions in influencing health disparities is not clear.” The importance of further research on this topic is underscored by the central finding of the study which found that the Appalachian region experiences considerable excesses in mortality from major causes of death and illness when compared to the rest of the nation. In addition, the study demonstrated significant within-region variability in mortality, hospitalization, behavioral risks, and socioeconomic conditions.