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Purpose:  We examined how substance use differed as a function of sex assigned at birth and gender identity (cisgender, transgender, or nonbinary/genderqueer) by type of substance. We sought to test whether current gender identity and sex assigned at birth were key factors in substance use among a large contemporary sample that included transgender and nonbinary/genderqueer adolescents.  Methods:  We analyzed data from a large national U.S. sample of sexual and gender minority (SGM) adolescents ( n  = 11,129) collected between April and December 2017. Chi-square tests of independence were used to test whether substance use behaviors varied by sex assigned at birth and gender identity. A series of multivariate logistic regression models tested the odds of substance use by sex assigned at birth and gender identity, as well as the interaction between sex assigned at birth and gender identity.  Results:  More than half of our sample reported lifetime alcohol use, and one-fourth of the sample reported lifetime marijuana use. Adolescents assigned male at birth had higher prevalence of substance use compared with adolescents assigned female at birth (AFAB). Multivariate models elucidated greater risk for most substance use outcomes for transgender adolescents compared with cisgender adolescents. We found significant interaction effects between gender identity and sex assigned at birth for recent alcohol use and lifetime and recent cigarette use among adolescents AFAB.  Conclusions:  These findings have implications for stakeholders who develop nationally representative surveys, researchers who examine substance use disparities among SGM adolescents, and mental health professionals who treat underage substance use among vulnerable populations.

Substance Use Among a National Sample of Sexual and Gender Minority Adolescents: Intersections of Sex Assigned at Birth and Gender Identity