Background: Warfarin is a crucial anticoagulant for CVDs (mechanical valve replacement, atrial fibrillation, pulmonary embolism and deep vein thrombosis). The complicated dosing schedules and frequent side effects of warfarin can negatively impact the health-related quality of life (HRQoL) of patients. Objectives: To assess the overall health-related quality of life (HRQoL) among patients on warfarin therapy and to identify the predictors associated with variations in HRQoL, using the WHOQOL-BREF and EQ-5D-5L instruments. Methods: A one year prospective observational study was conducted at KIMS Al Shifa Super Speciality Hospital .The study evaluated the quality of life of 93 patients taking warfarin using WHO-BREF and EQ-5D-5L scales. Patients received counselling and informational leaflets, with their knowledge evaluated before and after counseling. The study analyzed HRQoL ratings using descriptive statistics, such as mean and standard deviation. SPSS software version 25 was utilized to identify predictors of these scores. Result: The average EQ-VAS score was 75.69 ± 9.57, and the average EQ-5D index was 0.87 ± 0.12. The physical, psychological, social, and environmental domains had mean WHOQOL-BREF domain ratings of 20.36 ± 2.89, 18.52 ± 2.41, 10.92 ± 19.64, and 29.40 ± 3.17, respectively. Age, comorbidities, work status, and patient knowledge all showed significant disparities in HRQoL scores. Conclusion: Scores from the WHOQOL-BREF and EQ-5D-5L indicate that age, comorbidities, employment status, and patient knowledge significantly impact HRQoL, highlighting the need for personalized management and education for long-term warfarin users