Background: Health-related quality of life (HRQOL) is an important outcome measure in patients with end-stage renal disease (ESRD). HRQOL is assumed to improve with kidney transplantation and compared to hemodialysis. However, there is no evidence regarding HRQOL to support the optimal treatment choice for patients on hemodialysis who hesitate opting for transplantation. Therefore, this study aims to compare HRQOL between patients with ESRD and healthy individuals. Materials and Methods: This case-control study was performed of 50 patients with ESRD under hemodialysis and 100 healthy participants as controls. HRQOL was assess using the SF-36 questionnaire. Data was analysis by using linear regression to compared HRQOL between groups, and adjusted for age, gender, dialysis duration. Results: Most of the patients were males (62%) and aged 21 to 60 years old (82%). The patients and healthy subjects were significantly different in terms of the presence of chronic diseases (P<0.05). ESRD patients had a significantly lower level of satisfaction with health and function, family and friends, and social and psychological functions. The patients’ quality of life was not significantly affected by their demographic characteristics, including age, gender, educational level, marital status, and financial status. However, there was a significant association between chronic disease and HRQOL among ESRD (P=0.0001). Conclusion: ESRD has a remarkably negative effect on the patients’ quality of life and satisfaction with important domains of life. HRQOL among patients with end-stage renal disease can be affected by the associated chronic diseases. [GMJ.2020;9:e1987] DOI:10.31661/gmj.v9i0.1987