HIV/AIDS remains one of the most serious public health problems in Thailand. This study aimed to assess the health-related quality of life (HRQOL) and its related factors among people living with HIV/AIDS (PLWHA) in Thailand. A cross-sectional study was conducted with 259 patients at a tertiary care hospi­tal. HRQOL was assessed using the Thai version of the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire. Socio-demographics and clinical status were measured using a self-administered questionnaire. Multiple linear regression models were used to explore associations between socio-demographic status, clinical status, and HRQL. Multiple linear regression analyses showed that employment status was strongly related to better overall physical and men­tal health summary scores (PHS, MHS). In addition, patients with disclosure of HIV status, aged over 50 years, and having at least a rating of good health in the nurses’ opinion were the independent positive predictive factors for overall PHS. While being on antiretroviral therapy (ART) and good compliance with ART were positive predictive factors for overall MHS. Improving and strengthening quality of life among PLWHAs are important goals for HIV/AIDS services. Regular as­sessment of HRQL can provide potential information for intervention to improve quality of life.