Objectives. We assessed changes in cardiovascular disease-related health outcomes and risk factors among American Indians and Alaska Natives by age and gender. Methods. We used cross-sectional data from the 1995 to 1996 and the 2005 to 2006 Behavioral Risk Factor Surveillance System. The respondents were 2548 American Indian and Alaska Native women and men aged 18 years or older in 1995-1996 and 11104 women and men in 2005-2006. We analyzed the prevalence of type 2 diabetes, obesity, hypertension, cigarette smoking, sedentary behavior, and low vegetable or fruit intake. Results. From 1995-1996 to 2005-2006, the adjusted prevalence of diabetes among American Indians and Alaska Natives increased by 26.9%, from 6.7% to 8.5%, and obesity increased by 25.3%, from 24.9% to 31.2%. Hypertension increased by 5%, from 28.1% to 29.5%. Multiple logistic models showed no meaningful changes in smoking, sedentary behavior, or intake of fruits or vegetables. In 2005-2006, 79% of the population had 1 or more of the 6 risk factors, and 46% had 2 or more. Conclusions. Diabetes, obesity, and hypertension and their associated risk factors should be studied further among urban, rural, and reservation American Indian and Alaska Native populations, and effective primary and secondary prevention efforts are critical.