Introduction Acute myocardial infarction (AMI) affects patients’ health-related quality of life (HRQOL). AMI may decrease HRQOL, thus negatively affecting QOL. However, the improvements in interventional treatment and early rehabilitation after AMI may have a positive effect on HRQOL. Aim We evaluated HRQOL in patients after the first AMI treated in a reference cardiology centre in Poland and assessed which clinical variables affect HRQOL after AMI. Material and methods We prospectively evaluated HRQOL in 60 consecutive patients suffering after their first AMI during the index hospitalisation and again after 6 months, using: (i) MacNew, (ii) World Health Organization Quality of Life (WHOQOL) BREF, and (iii) Short Form (SF) 36. Results As measured by the MacNew questionnaire, global, social, and physical functioning did not change (p≥0.063), whereas emotional functioning improved 6 months after AMI, compared to index hospitalisation (p=0.002). As measured by WHOQOL BREF, physical health, psychological health, and environmental functioning did not change (p≥0.321), whereas social relationships improved 6 months after AMI (p=0.042). As assessed by SF-36, the global HRQOL improved after AMI (p=0.044). Patients with improved HRQOL in SF-36 often had a higher baseline body mass index (p=0.046), dyslipidaemia (p=0.046), and lower left ventricle ejection fraction (LVEF; p=0.013). LVEF<50% was the only variable associated with improved HRQOL in multivariate analysis (OR 4.463, 95% CI 1.045 - 19.059, p=0.043). Conclusions HRQOL increased 6 months after the first AMI, especially in terms of emotional functioning and social relationships. Patients with LVEF<50% were likely to have improved HRQOL.