BACKGROUND: Veterans Health Affairs (VA) home-based primary care (HBPC) is an evidence-based interdisciplinary approach to non-institutional long-term care that was developed in urban settings to provide longitudinal care for vulnerable older patients. Under the authority of a Memorandum of Understanding between VA and Indian Health Service (IHS) to improve access to healthcare, 14 VA medical centers (VAMC) independently initiated plans to expand HBPC programs to rural American Indian reservations and 12 VAMC successfully implemented programs. The purpose of this study is to describe barriers and facilitators to implementation in rural Native communities with the aim of informing planners and policy-makers for future program expansions. METHODS: A qualitative comparative case study approach was used, treating each of the 14 VAMC as a case. Using the Consolidated Framework for Implementation Research (CFIR) to inform an open-ended interview guide, telephone interviews (n = 37) were conducted with HBPC staff and clinicians and local/regional managers, who participated or oversaw implementation. The interviews were transcribed, coded, and then analyzed using CFIR domains and constructs to describe and compare experiences and to identify facilitators, barriers, and adaptations that emerged in common across VAMC and HBPC programs. RESULTS: There was considerable variation in local contexts across VAMC. Nevertheless, implementation was typically facilitated by key individuals who were able to build trust and faith in VA healthcare among American Indian communities. Policy promoted clinical collaboration but collaborations generally occurred on an ad hoc basis between VA and IHS clinicians to optimize patient resources. All programs required some adaptations to address barriers in rural areas, such as distances, caseloads, or delays in hiring additional clinicians. VA funding opportunities facilitated expansion and sustainment of these programs. CONCLUSIONS: Since program expansion is a responsibility of the HBPC program director, there is little sharing of lessons learned across VA facilities. Opportunities for shared learning would benefit federal healthcare organizations to expand other medical services to additional American Indian communities and other rural and underserved communities, as well as to coordinate with other healthcare organizations. The CFIR structure was an effective analytic tool to compare programs addressing multiple inner and outer settings.