Background: In 2001, the National Cancer Institute (NCI) funded a project to develop methods to recruit American Indian and Alaska Native (AI/AN) adults for a prospective cohort study of chronic disease risk and protective factors.Objective: We describe how the use of community-based participatory research (CBPR) principles led to more effective study design and implementation in a study in Alaska.Methods: CBPR elements included collaboration between researchers and tribes at all stages of the project, capacity building through training AI/AN staff in research methods, and knowledge dissemination through presentations, newsletters, and individual and community health feedback based on results of the study.Results: Between March 2004 and August 2006, 3,821 AI/ AN adults from 26 Alaskan communities enrolled in the study. Retention in the study is high, with over 88% of participants successfully completing a 2-year follow-up questionnaire.Conclusion: CBPR methods have facilitated effective development of study methods, recruitment and retention. Efforts are on-going to continue work with this unique AI/AN research participant community.