Objectives: American Indians (AIs) are over-represented among homeless populations, but are understudied regarding their unique risk and resilience factors relative to non-Hispanic white (NHW) adults experiencing homelessness. In the current study, we aimed to address this gap. Methods: We recruited participants (108 AIs and 307 NHWs) from 6 homeless serving agencies in Oklahoma City, OK. Participants completed standard assessments of health, health behaviors, including alcohol and drug use, readiness to change endorsed health behaviors (eg, unsafe sex, fruit and vegetable intake, happiness with weight, physical activity), sleep location and quality, personal victimization, and discrimination. Results: Compared to NHWs, AIs endorsed greater alcohol use problems and were more likely to report having been arrested/booked for disorderly conduct or public drunkenness; however, AIs were less likely to report smoking cigarettes and reported greater readiness to change unsafe/unprotected sexual behaviors. Furthermore, compared to NHWs, AIs reported experiencing greater discrimination and were more likely to report sleeping outside or on the streets, versus in shelters; however, AIs reported fewer days of inadequate sleep. Conclusions: Findings suggest AI-specific risk and resilience factors for homelessness. This information can aid in treatment, service, and housing planning for this under-studied group who experiences some of the greatest health disparities.