Background: Although acute myocardial infarction (AMI) was well treated and managed, it is one of the main factors increasing heart failure (HF) population. Sign and symptoms, and quality of life can be meaningful indicators to determine worsening disease in post AMI patients with impaired heart function. Purpose: The present study was conducted to identify the levels of sign and symptoms, self-care compliance, and health-related quality of life (HRQoL) in post AMI patients with low left ventricular ejection fraction (LVEF) during follow-up period, and to determine independent associating factors of HRQoL. Methods: A total of 91 post-AMI patients with LVEF < 50% at follow-up were recruited from outpatient department at a National University Hospital, and they were on medical treatment at least more than 1 year. Data were collected by individual interviews from July to September, 2011 using structured questionnaires of Heart Failure Symptom Checklist, Self-care Compliance for AMI patients, and Minnesota Living with Heart Failure Questionnaires. Results: Subjects��� mean LVEF was 41.0짹8.2% at follow-up and mean length of period after first cardiac event was 47.9짹24.4 months (range 21-171). The subjects who were belonged to New York Heart Association (NYHA) classification III & IV were 35.2% (n=32) and they reported averagely 4.8짹2.9 out of 13 HF symptoms. Stepwise multiple regression analysis showed that when age, gender, and time length after first AMI were controlled for, the number of sign and symptoms, lower education and higher NYHA classification significantly predicted lower level of HRQoL (Adjusted R2=0.526, p<.001). No significant relationship was found between self-care compliance and quality of life. Conclusion: We suggested that health care providers need to monitor carefully HF sign and symptoms for post AMI patients with lower LVEF to prevent impaired HRQoL and worsening of disease, especially for those with lower education.