Introduction. Research consistently shows that suicidal ideation and attempts are more prevalent among American Indian youth and young adults than youth and young adults in other racial/ethnic groups. Many of the associated psychosocial risk and protective factors are shared across racial/ethnic groups; however, for most of them, the prevalence is highest in American Indian youth. Research on the relation between suicide risk and culturally unique risk (e.g., childhood adversity, discrimination, parenting, unresolved grief, out-of-home placement) and protective factors (e.g., enculturation, cultural values, spirituality) in American Indian youth and young adults is limited. The goal of this research was to examine shared and culturally unique psychosocial risk and protective factors and coping strategies associated with suicide risk in American Indian youth and young adults.;Methods. Three interdependent cross-sectional studies were used to assess risk factors associated with suicidal ideation and attempts in Montana high school students using Youth Risk Behavior Survey (YRBS) data and to test a stress-coping model of suicide risk in American Indian tribal college students. In the first study, logistic regression was used to examine gender-specific individual-level risk factors associated with suicidal ideation/attempts for American Indian and White Montana high school students using pooled random sample secondary YRBS data. In the second study, logistic regression was used to identify gender-specific individual-level risk factors associated with suicidal ideation and attempts in American Indian students attending Montana reservation and urban high schools using pooled volunteer sample YRBS data. In the third study, logistic regression was used to test a stress-coping model (situated within a cultural-historical context) to determine associations between suicide risk and life stressors, coping skills, enculturation, cultural values, resilience, and social support in American Indian tribal college students in Montana and Wyoming using primary cross-sectional survey data.;Results. The primary results of the first study showed that American Indian youth had significantly more suicidal thoughts and attempts than the White youth. However, within YRBS risk factors, they had fewer statistically significant risk factors compared to the White youth. Sadness/hopelessness was the strongest, and the only statistically significant, risk factor of suicidal ideation/attempts shared across all four groups. The unhealthy weight control cluster was a significant risk factor for the White youth and the American Indian girls; alcohol/tobacco/ marijuana use was a significant risk factor only for the American Indian boys. Findings for the second study showed that the prevalence of suicidal ideation and suicide attempts did not differ significantly between reservation and urban American Indian youth. However, regression analyses showed differences and similarities in significant risk factors for ideation and attempts for girls and boys across the locations. Fewer differences were noted for girls than boys. Sadness/hopelessness was the only statistically significant risk factor for suicidal ideation and attempts common for girls and boys in both settings. Some form of violence (partner victimization, lack of school safety) was significantly and positively associated with either ideation and/or attempts in almost all groups. Partner victimization was significantly associated with both ideation and attempts for girls, but was inconsistent for boys. Lack of school safety was significantly associated with suicide attempts across the four groups, but was not a significant risk factor for ideation. Findings from the third study in Montana-Wyoming tribal college students revealed low levels of past year suicide risk. Culturally unique stressors such as adverse childhood experiences, parenting difficulties, thinking of historical losses, and discrimination were significantly and positively associated with suicide risk. Gratitude, social support, participant boarding school attendance, and higher current income mitigated suicide risk.;Conclusion. Results using the YRBS data show important differences in risk factor categories across the racial/ethnic and reservation-urban groups for girls and boys and indicate directions for future research targeting prevention and intervention. Results from the tribal college setting show important areas for future research and have implications for socioeconomic, structural, familial, and culture-based intervention development. A comprehensive understanding of culturally unique life stressors and cultural buffers is important to inform effective interventions and reduce suicide-related morbidity and mortality in his population.