Purpose: The purpose of this study was to explore factors that influence urban adolescent American Indian (AI) girls’ sexual risk behavior. Design: A qualitative study was conducted with grounded theory methodology to reveal factors and processes that influence sexual risk behavior. Method: Talking circles, individual interviews, and event history calendars were used with 20 urban AI 15- to 19-year-old girls to explore influences on sexual risk behavior. Results: The generated theory—framing sexual risk behavior—describes social and structural factors and processes that influenced the girls’ sexual risk behavior. The theory extends Bronfenbrenner’s ecological model by identifying microsystem, mesosystem, and macrosystem influences on sexual risk behavior. Discussion: Urban AI girls reported similar social and structural influences on sexual risk behavior as urban adolescents from other racial and ethnic groups. However, differences were noted in the family structure, cultural heritage, and unique history of AIs. Implications: This theory can be used in culturally responsive practice with urban AI girls.