<p>HIV/AIDS is a significant health issue on the global stage and has impacted more than 38&#xa0;million individuals. Despite the development of antiretroviral therapy (ART), socioeconomic barriers and stigma and discrimination can result in lower quality of life (QoL) in many people living with HIV (PLHIV). There is limited evidence on the determinants of QoL in PLHIV in Nepal. The purpose of the study was to evaluate QoL and its correlates among PLHIV who receive tertiary care services at hospitals in eastern Nepal. A cross-sectional study was conducted among 972 PLHIV aged 18 years and older who had been receiving ART for at least 6 months. A structured questionnaire consisting of sociodemographic, clinical, and psychosocial variables was used to collect data. The CES-D scale was used to measure depression, and the WHOQOL-HIV BREF tool was used to measure QoL. SPSS version 25 was used to analyze data, descriptive statistics, Pearson correlation, and ANOVA (<i>p</i> &lt; 0.05). The mean age of the participants amounted to 41.6 ± 10.6; 59.6% were men. The predictors of QoL (<i>p</i> &lt; 0.001) were education and employment in all domains. The QoL scores were positively correlated with urban residence and early clinical stage (<i>p</i> &lt; 0.05). Physician disclosure positively influenced all domains of QoL (<i>p</i> &lt; 0.001), and family disclosure negatively affected QoL (<i>p</i> &lt; 0.05). Physical and overall QoL had a positive correlation with comorbidities (<i>p</i> = 0.039 and <i>p</i> = 0.001). Socioeconomic, psychosocial, and clinical factors affect the QoL of PLHIV in Nepal. The stigma, encouraging positive disclosure, and enhancing socioeconomic stability are essential in helping to improve the welfare of PLHIV.</p>