Understanding gender-specific predictors of Health-related Quality of Life (HRQL) outcomes of HIV/AIDS treatment is necessary in the latent feminization of HIV epidemics in Vietnam. This study assessed HRQL and its predictors among men and women with HIV/AIDS. We conducted a cross-sectional study of 155 patients (36.8% women, mean age=31.4) registering for antiretroviral treatment (ART) at Vietnam-Sweden Uong Bi General Hospital, Quang Ninh Province. The Vietnamese version of the World Health Organization Quality of Life HIV brief version (WHOQOL-HIV BREF) was developed. Factor analysis was applied to assess the construct validity of the measurement. Six major domains of the Vietnamese WHOQOL-HIV BREF were determined, namely physical; performance; morbidity; environment; psychological; and social support. Internal consistency reliability of the six domains ranged from 0.52 to 0.71. Multivariate linear regression models, constructed using step-wise forward selection, determined different predictors of HRQL domain scores in men and women with HIV/AIDS. The results showed that men reported higher scores or better in Morbidity (p=0.02), Environment (p=0.07) and Psychological dimensions (p=0.02); meanwhile, women had higher scores in Performance (p=0.09). Alcohol and injection drug use negatively predicted HRQL outcomes in both men and women. Employment was associated with better performance in men, and better physical but poorer environment status in women. Female patients who have a child experienced decrements in social support, psychological, environment, and performance. Findings of this study highlight the need to develop comprehensive interventions for HIV/AIDS patients, including HIV/AIDS treatment support and gender-specific impact mitigation interventions strategies.