BACKGROUND: Indigenous youth experience disparities in health and education that lead to long-term hardship and poor health. Having a strong sense of cultural identity has been identified as a protective factor for Indigenous youth, although there is a need for empirical studies to further understand the relationship between cultural identity and health. Culturally-based after-school programs (ASPs) provide a valuable service that promotes health and wellbeing for Indigenous adolescents in an accessible setting. OBJECTIVES: The purpose of this dissertation was to investigate the relationship between cultural identity and health among American Indian adolescents. This investigation included the development, implementation, and evaluation of a culturally-grounded ASP located on an urban-based reservation community in Arizona. METHODS: The first stage consisted of a systematic review that identified culturally-based ASPs for Indigenous youth and synthesized evidence on reported health outcomes and outcomes related to intrapersonal constructs. The second stage focused on the formation and implementation of a culturally-grounded ASP, Native Spirit (NS), in partnership with the Boys & Girls Clubs of Greater Scottsdale (BGC) and the Salt River Pima-Maricopa Indian Community (SRPMIC). The third stage used a mixed methods approach to evaluate the impact of participation in the NS program on cultural identity, self-esteem, and resilience in American Indian (AI) adolescents (grades 7-12). RESULTS: The systematic review identified 9 articles representing 9 different ASPs that met the inclusion criteria and then were critiqued. Primary outcomes included substance abuse, cultural identity, and intrapersonal constructs including self-efficacy, self-concept, and self-esteem. The NS partnership, described in stage two, resulted in the development of a 13-session culturally-grounded ASP that focuses on local cultural values and practices. Each session is facilitated by 1-2 local cultural practitioners and community leaders. The stage three evaluation showed increases in mean strength in cultural identity, resilience and self-esteem between baseline and posttest evaluation. Themes related to benefits of participating in the program included curiosity and commitment to cultural identity, increases in confidence and self-esteem, and ability to overcome challenges and build resilience. CONCLUSIONS: The current study provided additional evidence of the positive impact that strength in cultural identity imparts on the health and wellbeing of AI adolescents. These findings also highlighted unique opportunities for health promotion with collaborations with BGCs and after-school programs.