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This study tested direct and indirect associations between minority stressors and psychological distress in a large, geographically diverse sample of transgender individuals (N = 1,207). Transgender individuals were recruited for an online, cross-sectional survey using targeted sampling. Structural equation modeling was used to test the hypothesized model, which was based on Hatzenbuehler’s (2009) integrative mediation framework. Expectations of rejection, self-stigma, and prejudice events were all associated with psychological distress, and these relationships were partially accounted for by rumination. This model had good fit (Tucker-Lewis Index = .96, Comparative Fit Index = .98, Root Mean Square Error of Approximation = .05, 90% CI [.05, .06]) and explained 54.5% of the variance in psychological distress and 29.3% in rumination. This is the first study to examine a model of minority stress and psychological distress that includes rumination and all four minority stressors from Meyer’s (2003) framework in a large sample of transgender individuals. Results indicate a strong relationship between minority stressors and psychological distress among transgender people, and that these relationships are partially explained by rumination. Results need to be considered in relation to the cross-sectional nature of the design and the possible role for additional variables. Future research should investigate these findings using designs that provide tests of causality.