The objectives of this study were to evaluate the quality of life of people living with HIV/AIDS and its relationship with clinical factors. This cross-sectional analytical study was performed with a non-probabilistic sample, consisting of people living with HIV/AIDS and undergoing clinical and outpatient treatment in two health services specialised in AIDS care in the municipal healthcare network of Ribeirão Preto, São Paulo, Brazil. Data collection was performed by means of individual interviews using a script for the sociodemographic and clinical characterization, and the HIV/AIDS-targeted quality of life instrument (HATQoL). The participants were 228 individuals living with HIV/AIDS, 122 (53.5%) men and 106 (46.5%) women, with a mean age of 39 years. Regarding the clinical variables, it was identified that the participant’s time of awareness regarding the HIV diagnosis was related to a poorer quality of life (QL) in several domains. The immunological condition is one of the variables that was related with a better QL, as individuals with a CD4 cell count greater than 500 cells/mm³ showed better means with statistically significant differences in five domains: overall activity, health worries, HIV mastery, life satisfaction, and medication worries. Furthermore, it was identified that individuals with AIDS had lower scores with significant differences in the domains: overall function and disclosure worries. Understanding the variables related to the QL of people living with HIV/AIDS is key, considering the chronic evolution of the infection, the possibility of treatment, greater survival and dealing better with the disease. The clinical variables should be continually monitored by the health team considering that the clinical and/or immunological condition is related to several aspects such as adherence to treatment, evolution of the infection, physical and mental health condition, as well as quality of life.