IntroductionAlcohol use disorder (AUD) and tobacco use disorder (TUD) are more severe among some sexual minority subgroups. It is less understood whether mental health indicators also differ by sexual identity among those with more severe forms of AUD and TUD. We examined differences in mental health-related QoL by sex-specific sexual identity subgroup among those meeting criteria for moderate-to-severe AUD or moderate-to-severe TUD. MethodsWe analyzed data from the National Epidemiologic Study of Alcohol and Related Conditions-III (2012–2013; n = 36,309). Our analyses focused on those meeting criteria for past-year moderate-to-severe AUD (n = 2341) and past-year moderate-to-severe TUD (n = 3675). Using multivariable linear regression, we examined associations of sex-specific sexual identity subgroups with mental health-related QoL, while controlling for (a) sociodemographic characteristics, (b) disorder severity, and (c) risk and protective factors (adverse childhood experiences, parental history of substance misuse, stressful life events, and social support). ResultsAmong those with past-year moderate-to-severe AUD, gay men and heterosexual, bisexual, and gay/lesbian women had significantly lower mental health-related QoL compared to heterosexual men in fully adjusted models. Among those with past-year moderate-to-severe TUD, gay men and heterosexual and gay/lesbian women had significantly lower mental health-related QoL compared to heterosexual women. Bisexual and heterosexual women were not significantly different in fully adjusted models. DiscussionClinicians should consider the variability in mental health-related QoL among those with moderate-to-severe AUD and TUD particularly for women and sexual minorities. Consideration of current and past stressors and the degree of social support may be beneficial when conducting assessments and forming treatment plans.