Engaging communities is highly recommended in the conduct of health research among vulnerable populations. The strength of community-engaged research is well documented and is recognised as a useful approach for eliminating health disparities and improving health equity. In this article, five interdisciplinary teams from the Medical University of South Carolina present their involvement with community-engaged research with a unique population of Gullah African Americans residing in rural South Carolina. Their work has been integrated with the nine established principles of community-engaged research: establishing clear goals, becoming knowledgeable about the community, establishing relationships, developing community self-determination, partnering with the community, maintaining respect, mobilising community assets, releasing control, and maintaining community collaboration. In partnership with a Citizen Advisory Committee, developed at the inception of the first community-engaged research project, the academic researchers have been able to build on relationships and trust with this population to sustain partnerships and to meet major research objectives over a 20-year period. Challenges observed include structural inequality, organisational and cultural issues, and lack of resources for building sustainable research infrastructure. Lessons learned during this process include the necessity for clearly articulated and shared goals, knowledge about the community culture, and embedding the cultural context within research approaches. Keywords: Engaged health research, vulnerable populations, longterm collaboration, South Carolina 'Gullah' communities