The aim of the study is to explore the factors those differentiate health related quality of life (HRQOL) among hepatitis B (HBV) and hepatitis C (HCV) patients. Different public and private hospitals of Sargodha district were visited and 120 patients of hepatitis B and C were interviewed. World health related quality of life-BREF (WHOQOL-BREF) questionnaire was used to construct HRQOL instrument. Multiple regression analysis was performed to observe the collision of demographic, medical, economic and physical and psychological factors on patients HRQOL. Results showed that HBV patients enjoyed better HRQOL then HCV patients. 86.4% HCV patients faces death threat while, 67.3% HBV faces this threat. 93.5% HBV patients feels depression while, 97.8% HCV patients feels depression. Urban patients HRQOL scores were superior then rural patients in both HCV and HBV case. Moreover, male patients HRQOL scores were better as compared to female patients. Age of the patient, disease severity, use of drug, pain, depression, financial hindrance and threat of death negatively influence the HRQOL of both HBV and HCV patients while, vaccination, income, sleep, opportunity of leisure and better living condition were positively related to HRQOL.