Objective: Posttraumatic stress symptoms are very high among sexual and/or gender minority (SGM) people. Development and testing of trauma interventions with SGM people is needed, but first we need to understand who among SGM people are at greatest risk of posttraumatic stress symptoms, how minority stress may contribute, and the frequency of substance use comorbidity with significant posttraumatic stress symptoms among SGM people. Method: General linear models and logistic regressions were used to examine demographic differences, minority stress, and substance use related to posttraumatic stress symptoms among a national sample of SGM people (N = 4,589, Mage = 32.1, 55% cisgender). Results: All gender groups had greater posttraumatic stress symptoms than the reference group of cisgender men. All sexual orientation groups, except for straight/heterosexual SGM people, had greater posttraumatic stress symptoms than participants in the reference gay/lesbian group. Younger age and identifying as American Indian or Alaska Native and Hispanic, Latino, or Spanish was associated with more posttraumatic stress symptoms. Non-specific and SGM-specific minority stress were each related to greater odds of significant posttraumatic stress symptoms, even after accounting for Criterion A events. Among participants with significant posttraumatic stress symptoms, 13.6% were at risk for alcohol use disorder, and 56.4% were at risk for other substance use disorder. Conclusions: Marginalized SGM subgroups have more posttraumatic stress symptoms. Interventions for SGM people should consider minority stress coping strategies and substance use comorbidities.