The Strong Heart Study (SHS) is a longitudinal observational study of two combined cohorts followed prospectively: the original SHS cohort recruited in 1989 to 1991 and a Strong Heart Family Study (SHFS) cohort recruited in 1998 to 1999. The original and family cohorts together form the largest, multicenter, prospective epidemiological study of cardiovascular disease (CVD) in Native Americans/ American Indians. The study’s main objective is to examine the etiology and natural history of cardiovascular disease in Native Americans/American Indians. The study involves a partnership with 12 Tribal Nations who live in Arizona, Oklahoma, and the Dakotas.