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OBJECTIVE. ESTEEM (Effective Skills to Empower Effective Men) represents the first intervention to address the psychological pathways through which minority stress undermines young sexual minority men’s (SMM’s) mental and sexual health using transdiagnostic cognitive- behavioral therapy. This study compared the efficacy of ESTEEM against two existing interventions. METHOD. Participants were young HIV-negative SMM (N=254; ages 18-35; 67.2% racial/ethnic minority) experiencing a depression, anxiety, and/or stress-/trauma-related disorder and past-90-day HIV-transmission-risk behavior. After completing HIV testing and counseling, participants were randomized to receive 10-session ESTEEM (n=100); 10-session community-based LGBQ-affirmative counseling (n=102); or only HIV testing and counseling (n=52). RESULTS. For the primary outcome of any HIV-transmission-risk behavior at 8-months, ESTEEM was not significantly associated with greater reduction compared to HIV testing and counseling (RR=0.89, p=0.52). Supportive analyses of the frequency of HIV-transmission-risk behavior at 8-months showed a non-significant difference between ESTEEM compared to HIV testing and counseling (RR=0.69) and LGBQ-affirmative counseling (RR=0.62). For secondary outcomes (e.g., depression, anxiety, substance use, suicidality, number of mental health diagnoses) at 8-months, ESTEEM had a larger effect size than the two comparison conditions, but these comparisons did not reach statistical significance when adjusting for the false discovery rate. Observed effect sizes for condition comparisons were smaller than the effect sizes used to power the study. In exploratory analyses, ESTEEM showed promise for reducing comorbidity. CONCLUSIONS. Because the control conditions were associated with stronger effects than anticipated, and given the heterogeneous nature of transdiagnostic outcomes, the study possessed insufficient power to detect the consistently small-to-moderate benefit of ESTEEM compared to the two control conditions.