The Strong Heart Study (SHS) is a large, multi-community study to investigate the high incidence of cardiovascular disease (CVD) among American Indians and to improve long-term health outcomes within the communities. CVD is the No. 1 cause of death for three geographically and culturally diverse American Indian populations. The SHS investigated the prevalence and incidence of CVD as well as the distribution of risk factors in members of 13 American Indian tribes in Oklahoma, Arizona, and (as one region) North and South Dakota. The SHS enrolled more than 4500 participants ranging in age from 45 to 74 years. During the three-phase study, which began with baseline examinations from 1989 through 1991 and concluded in 1999, participants received medical examinations in each phase. To build trust and cooperation, SHS investigators worked closely with tribal leaders and community members, including establishing empowered committees and hiring community members for jobs within the study. As a result of such cooperation, the SHS maintained retention rates of about 90% across all three phases. Benefits to tribal communities also included health care improvements and education for healthy lifestyles. The SHS could serve as a model for similar studies of American Indians or other minority groups.