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This study examined the 2013 New Mexico Youth Risk and Resiliency Survey (NM-YRRS) to determine whether cultural connectedness and positive relationships with adults protected against suicide attempts among American Indian and Alaska Native (AI/AN) youth and whether these relationships differed by gender. The sample included 2,794 AI/AN students in grades 9 to 12 who answered the question about past-year suicide attempts. Protective factor variables tested included relationships with adults at home, school, and the community. The language spoken at home was used as a proxy measure for cultural connectedness. Positive relationships with adults were negatively associated with the prevalence of past-year suicide attempts in bivariate analysis. However, language spoken at home was not associated with the prevalence of suicide attempts. Multivariate analysis showed that among girls, relationships with adults at home, at school, and in the community were independently associated with lower suicide-attempt prevalence. Among boys, only relationships with adults at home showed such an association. These results have important implications for the direction of future research about protective factors associated with AI/AN youth suicide risk as well as in the design of suicide intervention and prevention programs.