Background: We describe the prevalence of behaviors that put American Indian and Alaska Native (AI/AN) high school students at risk for teen pregnancy and sexually transmitted infections (STIs) and the relationships among race/ethnicity and these behaviors. Methods: We analyzed merged 2007 and 2009 data from the national Youth Risk Behavior Survey, a biennial, self-administered, school-based survey of US students in grades 9-12 (N?=?27,912). Prevalence estimates and logistic regression, controlling for sex and grade, were used to examine the associations between race/ethnicity, and substance use, and sexual risk behaviors. Results: Of the 26 variables studied, the adjusted odds ratios (AOR) were higher among AI/AN than White students for 18 variables (ranging from 1.4 to 2.3), higher among AI/AN than Black students for 13 variables (ranging from 1.4 to 4.2), and higher among AI/AN than Hispanic students for 5 variables (ranging from 1.4 to 1.5). Odds were lower among AI/AN than Black students for many of the sexual risk-related behaviors. Conclusions: The data suggest it is necessary to develop targeted, adolescent-specific interventions aimed at reducing behaviors that put AI/AN high school students at risk for teen pregnancy, STI/HIV, and other health conditions.