Abstract: Major changes to lifeways, such as settlement organization and subsistence economy, may have profound and long-lasting effects on the existence and survival of any society. This thesis uses broad-scaled but fine-grained paleopathological analysis to more fully understand a period of substantial cultural, social, and environmental change that occurred during the Late pre-Columbian period (AD 900–1600) in the Eastern Woodlands of North America. These changes were initiated by the Mississippian cultural phenomenon between AD 1000 and 1600. Specifically, this research analyzes a skeletal collection derived from one of the largest Mississippian period communities in the lower Ohio River valley, the Angel site (12Vg1). While large-scale excavations occurred at Angel in the early and mid-20th century, many aspects of life in this community remain unclear. A novel view of Angel is provided in this work, as it is the first to conduct a full skeletal analysis of the collection. This thesis has the unique ability to provide much-needed data concerning the processes behind the adoption of Mississippian lifeways specific to this region. Angel paralleled the sociocultural complexity of other mounded sites in the Eastern Woodlands but developed in an understudied area with regards to skeletal remains, the lower Ohio River valley. This research adds to this body of knowledge. The pathologies examined in this research were specifically selected to explore various aspects of life influenced by the Mississippian culture. This study shed light on the impact of population aggregation, a heavy reliance on maize agriculture, the risk of bodily harm associated with daily activities and violent interactions, and overall levels of biological stress at Angel. The broader impact of this research centers on its examination of a skeletal legacy collection that has been curated for over 70 years and is currently in the process of repatriation. This work is the last to directly examine the people who inhabited, created, and experienced the Angel community.