Introduction: Decrements in health-related quality of life (HRQOL) and sexual difficulties are a recognized consequence of prostate cancer (PCa) treatment. However little is known about the experience of gay and bisexual (GB) men. Aim: HRQOL and psychosexual predictors of HRQOL were examined in GB and heterosexual men with PCa to inform targeted health information and support. Method: One hundred twenty-four GB and 225 heterosexual men with PCa completed a range of validated psychosexual instruments. Main outcome measure: Functional Assessment of Cancer Therapy e Prostate (FACT-P) was used to measure HRQOL, with validated psychosexual measures, and demographic and treatment variables used as predictors. Results: GB men were significantly younger (64.25 years) than heterosexual men (71.54 years), less likely to be in an ongoing relationship, and more likely to have casual sexual partners. Compared with age-matched population norms, participants in both groups reported significantly lower sexual functioning and HRQOL, increased psychological distress, disruptions to dyadic sexual communication, and lower masculine self-esteem, sexual confi- dence, and sexual intimacy. In comparison with heterosexual men, GB men reported significantly lower HRQOL (P ¼ .046), masculine self-esteem (P < .001), and satisfaction with treatment (P ¼ .013); higher psychological distress (P ¼ .005), cancer related distress (P < .001) and ejaculatory concern (P < .001); and higher sexual functioning (P < .001) and sexual confidence (P ¼ .001). In regression analysis, psychological distress, cancerrelated distress, masculine self-esteem, and satisfaction with treatment were predictors of HRQOL for GB men (R2 Adj ¼ .804); psychological distress and sexual confidence were predictors for heterosexual men (R2 Adj ¼ .690). Conclusion: These findings confirm differences between GB and heterosexual men in the impact of PCa on HRQOL across a range of domains, suggesting there is a need for GB targeted PCa information and support, to address the concerns of this “hidden population” in PCa care.