The overall goal of this correlational study was to evaluate the health-related quality of life (HRQoL) of women 50 years old or older with HIV/AIDS and its association with sociodemographic, clinical and psychosocial factors. The sample comprised 200 women who were monitored clinically at three clinics of Specialized Outpatient STD/AIDS Services in the municipality of São Paulo. The study was approved by the Research Ethics Committee of the São Paulo Municipal Department of Health (Reports nos. 09/2010 and 66/2010). After signing a Free and Informed Consent Form, the women were interviewed individually in a private room and answered the following instruments: a Sociodemographic and Clinical Characterization, Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12), HIV/AIDS-Targeted Quality of Life Instrument (HAT-QoL), the Rosenberg Self-Esteem Scale and the Herth Hope Index. The data were collected between February and July 2010 and were analyzed statistically, including descriptive, reliability and correlation analysis of the instruments, a comparison of averages and a logistic regression analysis. The results revealed a greater involvement of HRQoL in the domains of Disclosure Worries (30.65 ±30.22) and Financial Worries (35.50 ±35.97), and better scores in the domains: Provider Trust (79.79 ±21.27) and Medication Worries (76.49 ±21.06) of the HAT-QoL. In addition, a significant positive correlation was found between the components of the SF-12 and five domains of the HAT-QoL; between the components of the SF-12 and the hope and self-esteem scores; and between the HAT-QoL domains and hope (except for two domains) and self-esteem (except for two domains) scores. A comparison of the average values of HRQoL based on sociodemographic, clinical and psychosocial factors revealed a statistical association among sociodemographic (marital status, education and per capita income), clinical (self-perception of health status, viral load, CD4, time of awareness of the presence of HIV, current status of the disease, the use and time of antiretroviral therapy and how she feels about the treatment) and psychosocial (selfesteem and hope) factors. The logistic regression indicated that, in general, a higher monthly income per capita, a CD4 count above 200 cells/mm 3 , the use of antiretroviral medication/drugs, long-term awareness of the HIV infection, a good to excellent perceived health status, and higher levels of hope and self-esteem all contribute to improve the HRQoL of women 50 years or older suffering from HIV/AIDS. Therefore, it is concluded that sociodemographic, clinical and psychosocial factors influence the HRQoL of the women under study.