ABSTRACT People with disabilities are significantly more likely to experience chronic conditions and are at risk of dying up to 20 years earlier than people without disabilities due to physical, social, psychological, and financial challenges. Appalachian Kentucky, a rural area with limited healthcare access, has twice the U.S. rate of disability—22.7% compared with 12.6% nationally. Rates of new or “acquired disability” are escalating as medical advances allow more people to survive hospitalization and live with disability, yet we lack the knowledge to help people live well post-hospitalization. Specifically, while formal medical care plays an invaluable role in saving the lives of people who experience an acute health event, these survivors and their families are often left to manage the enduring challenges of living with acquired disability on their own. I propose a mixed methods ethnographic investigation to understand the nature of acquired disability, including subsequent care throughout the life course, in the rural communities of Appalachian Kentucky. Ethnographic studies enable a holistic—personal, environmental, sociocultural, and political—perspective to understand individuals’ lived experiences and identify opportunities to reduce adverse health outcomes. Long-term health is intimately intertwined with broader cultural and structural factors that contribute to significant health challenges for rural, disabled populations, including informal (family and social relations), formal (health and human services), and institutional (policy and programs) forms of care. Consistent with the socioecological model, I will identify multilevel factors impacting quality of life and long-term health and identify strategies to reduce stressors. Obtaining grounded insights on how disability amplifies existing challenges is necessary to inform health, policy, and structural interventions to improve quality of life and long-term health for people with disabilities. I propose two related aims: (1) to ethnographically investigate and describe experiences of acquired disability among those with disabilities, family caregivers, health and human service providers and policymakers and (2) to develop and verify a shared cultural model of disability describing the range of barriers, facilitators, and opportunities to help rural Appalachians live well with disability. To achieve these aims, I will obtain rigorous training in rapid ethnographic assessment, concept mapping, culturally adapted interventions, and grant writing to support my growth as an independent health equity researcher. A robust understanding of disability based on grounded experiences will inform future culturally adapted interventions to mitigate health challenges and improve the lives of people with disabilities and their families.