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Heart failure is a challenging public health problem associated with poor health-related quality of life (HRQoL). Data on the quality of life of people with heart failure are limited in Ethiopia. This study aimed to assess the HRQoL and its influencing factors in people with heart failure in Ethiopia. A hospital-based, cross-sectional study design was conducted in the cardiac outpatient clinics of two tertiary-level hospitals in Addis Ababa, Ethiopia. Data were collected from people with heart failure who met the inclusion criteria using an interviewer-administered questionnaire. The HRQoL was measured using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). A multiple linear regression model was fitted to identify factors that influenced HRQoL. All statistical analyses were conducted using STATA version 17 software. A total of 383 people with heart failure participated in the study. The mean age of the participants was 55 years. The MLHFQ score was 48.03±19.73, and 54% of participants had poor HRQoL. Multiple linear regression analysis revealed that age (β= 0.12, 95% CI 0.11, 0.28), diabetes mellitus comorbidity (β= 4.47, 95% CI 1.41, 7.54), social support score (β= − 1.48, 95% CI − 1.93, − 1.03), and depression score (β = 1.74, 95% CI 1.52, 1.96) were significant factors influencing overall HRQoL (p < 0.05). This study found that people in Ethiopia with heart failure had poor HRQoL, influenced by several factors. The findings can help health professionals identify appropriate interventions to improve the HRQoL of people with heart failure. [ABSTRACT FROM AUTHOR]