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Background: Measurement of medication adherence and health-related quality of life is extremely important when planning different health policies. Drug therapy and adherence to medication are critical to prevent complications of hypertension, especially in countries like Nepal, where hypertension is one of the most prevalent diseases. However, this has not been studied in Nepal. This study, hence, aimed to explore medication adherence, factors affecting medication adherence, health-related quality of life, and the correlation between medication adherence and health-related quality of life in hypertensive patients visiting tertiary care health facilities in Lalitpur district of Nepal. Methodology: This quantitative cross-sectional study was conducted among 380 hypertensive patients at KIST Medical College and Teaching Hospital, Lalitpur, Nepal. The Nepali version of the European Quality of Life tool EQ-5D-5L and the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HBCTS) were used. Intergroup differences in medication adherence, the EQ-5D index and EQ-VAS scores were assessed for statistical significance using either the Mann–Whitney or Kruskal–Wallis tests for numerical data. Spearman correlation coefficient was used to identify the relationship among medication adherence, EQ-5D-5L index values, and EQ-VAS scores. Results: The mean treatment score was 22.43 ± 4.12. Age, sex, and occupation were significant factors that affected treatment adherence. The EQ-5D score was 0.72 with age, sex, income, and educational status as significant factors and marital status as an insignificant factor. A slightly negative correlation was found between the total treatment adherence score and the EQ-5D index. Conclusion: The treatment adherence of patients to antihypertensive therapy was suboptimal, which could affect the outcome of therapy. Better treatment adherence was correlated with a better health-related quality of life. Hence, both health-care providers and patients should make efforts to increase treatment adherence to attain better HRQOL. [ABSTRACT FROM AUTHOR]