Introduction: Acquired immunodeficiency syndrome (AIDS) has evolved from a mysterious illness to a global pandemic which has infected tens of millions of people. Assessing health-related quality of life (HQOL) is useful for documenting the patients' perceived burden of chronic disease, tracking changes in health over time, assessing the effects of treatment and quantifying the return on health care investment. The study aimed to assess the quality of life and its associated factors in patients with HIV/AIDS. Material and methods:It was a hospital-based observational study conducted at the anti-retroviral therapy centre of the civil hospital, Nashik District. A total of 100 participants with confirmed HIV/ AIDS were included. The WHOQOL-HIV BREF instrument was used to assess the quality of life of people living with HIV/AIDS (PLHAs). Multivariate logical regression was used to study the factors affecting the quality of life of PLHAs. Results:The mean scores of HQOL was highest in the domain of spirituality (15.99) followed by the physical domain (14.71), level of independence (14.45), social relationships (14.04), psychological domain (13.26), and environment (13.04), and the overall perception of quality of life and general health perception's scores were 13.28 and 12.84. Conclussions:These findings highlight the need for enhanced socio-psychosocial support and a better environment for improving the health-related quality of life among PLHAs.