Introduction. Myocardial infarction is the most frequent manifestation of coronary heart disease and one of the leading causes of death worldwide. The sudden and often profound physiological and psychological effect of the acute onset of myocardial infarction hurts the health-related quality of life. Objective. To assess health-related quality of life and associated factors among myocardial infarction patients at Cardiac Center, Ethiopia, Addis Ababa, Ethiopia, 2020. Method. Institution-based cross-sectional study was conducted from April 10 to June 25, 2020, at the Cardiac Center-Ethiopia, Addis Ababa, Ethiopia. The sample consisted of 421 myocardial infarction patients. Data were collected through an interviewer-administered structured questionnaire by using the World Health Organization Quality of Life Questionnaire. Samples were selected using a consecutive sampling technique. The linear regression analysis model was fitted using SPSS 26 and STATA 14, and the unstandardized beta (š½) coefficient with a 95% confidence interval was used. A
p
value <0.05 was considered statistically significant for all analyses. Results. The mean score of the overall health-related quality of life was found to be
49.29
Ā±
14.83
, and the mean score for the physical domain was
47.96
Ā±
16.50
; for the psychological domain, it was
50.91
Ā±
16.07
, and for environmental and social relationship domains, it was
48.30
Ā±
16.54
and
52.02
Ā±
24.61
, respectively. In the multiple regression analysis, increased age, living in a rural area, heart failure, and hypertension were inversely associated with overall health-related quality of life, while secondary and higher education were associated with better overall health-related quality of life. Conclusion. Patients with myocardial infarction at Cardiac Center, Ethiopia, had lower health-related quality of life. Hence, the finding of this study suggests the implementation of a cardiac rehabilitation program and comprehensive service given by healthcare providers.