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Introduction Acute myocardial infarction has negative influence on patient's quality of life. The objective of the paper was to assess the health-related quality of life in the patients one month and twelve months after acute myocardial infarction and to compare it with the healthy controls. Material and Methods A prospective cohort study involved 160 patients aged from 30 to 79 and 240 healthy controls. The health-related quality of life was assessed with the Serbian version of these questionnaires: Euro- Quol-5-Dimension and EuroQuolVAS. Angina pectoris was ranked according to the classification of Canadian Cardiovascular Society. Multivariate logistic regression analysis was used. Results The healthy controls had significantly higher average scores in EuroQuolVAS compared with the patients one month after acute myocardial infarction (74.35±9.42 vs 60.50±12.03, p<0.001), as well as twelve months afte acute myocardial infarction (74.35±9.42 vs 69.83±12.06, p<0.001). Significantly lower average ranges in EuroQuol-5-Dimension questionnaire and higher quality of life were found twelve months after acute myocardial infarction than one month after acute myocardial infarction (1.41±0.26 vs 1.53±0.26, p<0.001). The average ranges of angina pectoris were significantly lower in all the patients twelve months after acute myocardial infarction compared with the first month (0.78±0.51 vs 0.91±0.44, p<0.001). The multivariate regression analysis confirmed thrombolytic therapy, percutaneous transluminal angioplasty and age to be important factors influencing health-related quality of life. Conclusion The patients assessed their health condition to be significantly higher twelve months after acute myocardial infarction than one month after it. The health-related quality of life was significantly higher in patients who had undergone the percutaneous intervention than in those who had been treated with the thrombolytic therapy. [ABSTRACT FROM AUTHOR]