Quality of life (QoL) is an important component in the evaluation of the wellbeing of people living with HIV/AIDS (PLHIV). This study was aimed at evaluating the QoL of PLHIV attending the antiretroviral clinics in the Ho municipality. A cross-sectional study was conducted from January 2017 to April 2017 involving 158 purposively selected HIV-positive patients who were attending the antiretroviral clinics both in the Volta Regional Hospital and Ho Municipal Hospital. An Interviewer administered standard questionnaire (WHOQOL-HIV Bref) was used to collect information on sociodemography, medical history, and the quality of life (QoL) of the respondents. Among these 158 HIV-positive respondents, 126 (79.75) and 14 (8.86) presented with excellent and good overall QoL, respectively, whilst 18 (11.39) had their life negatively affected by HIV/AIDS. Religious/personal beliefs (19.62%) were the most affected QoL component, followed by the physical (15.82%) and level of independence (15.19%) domains. Patients' occupation, perception of health, sexual activity, and state of the disease were associated with poor overall QoL. In general, being an HIV-infected man, symptomatic patient, not being sexually active, or being ART naïve was also associated with poorer QoL in several HIV/AIDS QoL domains.