Objectives: This paper presents findings from a research partnership with rural American Indian communities to identify protective factors associated with their adolescents' health-related behaviors including 1) delay of sexual debut; 2) not having had intercourse in the past 3 months; 3) birth control use among sexually active adolescents in the past 3 months; 4) condom use in the past 3 months. Our goal was to identify salient characteristics of students and their perceptions of family, school, and friends which could be incorporated or supported in future program planning for adolescents. Methods: A written survey was administered to 484 Indian students in Grades 6–12 from five rural schools. The survey measured several potential protective factors identified by Problem Behavior Theory, along with self-efficacy and cultural interest and knowledge. Logistic regression assessed the relationship of the protective factors and positive sexual behaviors. Results: Factors significantly associated with abstention from intercourse and/or consistent use of birth control included perceived lower health-risk behavior of friends, higher perceived parental support, higher perceived parental knowledge and monitoring of the adolescent's activities and friends, a higher value on scholastic achievement, higher reported academic performance, and higher self-efficacy for safer sexual behaviors. Conclusions: This research suggests that Indian adolescents have several protective factors indigenous to their communities which are modifiable. Building on the unique cultural heritage of Indian communities, many of these factors may be addressed through community planned prevention programs.