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Assessment of health-related quality of life (HRQOL) in resource-limited settings is critical to evaluate and improve the burden of morbidity and mortality associated with chronic medical disorders. There is a dearth of data on HRQOL among patients suffering from chronic medical disorders in Nigeria. This study assessed the HRQOL of participants with diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, and cancer in a hospital setting with limited resources and highlighted associated factors.