Adults aged 65 years and above have grown substantially over with past decade. However, the chance of developing multiple comorbidities only increases with age. Because elderly residents of rural Appalachia often encounter barriers to healthcare, rural nurses, providers, and policy makers must overcome physical and structural barriers, but also gain a more in-depth understanding of the personal and cultural attitudes impacting the use of new and innovative forms of healthcare delivery. With a slow and variable uptake of telehealth adoption in rural Appalachia, and in the presence of well-documented medical mistrust, this study was designed to better understand the degree of medical mistrust existing in the elderly of rural Appalachia and to assess if medical mistrust may be inhibiting efforts related to telehealth acceptance. A correlational design was utilized administering the Medical Mistrust Index (MMI) and Technology Acceptance Model (TAM) questionnaire via electronic survey to those age 65 years and above living in rural Appalachia. Deemed well-established and validated, the MMI measures medical mistrust from a broader perspective, while TAM assesses telehealth acceptance in terms of perceived usefulness, perceived ease of use, and overall attitude towards telehealth as a technology. Demographics of gender, income, education, and previous telehealth experience were compared to MMI and TAM scores. The study revealed a moderate level of medical mistrust and telehealth acceptance among the elderly of rural Appalachia. A statistically significant negative relationship was found between MMI and TAM for those reporting previous telehealth experience, and among all demographics, with the strongest correlations found among females and participants of lower education. Elderly rural Appalachians have a rich social and cultural history, but past experiences and long-held beliefs have resulted in medical mistrust and slow telehealth uptake. Stakeholders have a responsibility to meet individuals where they are understanding that elderly residents of rural Appalachia may not be ready or fully prepared to incorporate telehealth into their management of care. However, quality rural nursing practice and continued research has the ability to evolve to meet the needs that exist among those of advancing age with limited healthcare resources such as those found in rural Appalachia.