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OBJECTIVE To determine the relationship of serial interferon (IFN) measurements and adverse cardiac remodeling (AR) after myocardial infarction (MI). STUDY DESIGN Observational multi-centre study. PLACE AND DURATION OF STUDY Departments of Cardiology of Diskapi Yildirim Beyazit Training and Research Hospital, Ataturk Training and Research Hospital, Numune Training and Research Hospital, and Dr. Nafiz Sincan Korez State Hospital, Turkey, from June 2015 to June 2020. METHODOLOGY Forty-seven patients with acute MI were included. IFN levels were measured on the first day and at 14 days and 45 days post-MI. Reverse cardiac remodeling (RR) and AR were defined as the reduction of left ventricular end-diastolic volume by ≥12% and increases of ≥12% by cardiac magnetic resonance imaging at the 6-month follow-up. Statistical significance was accepted as p<0.05. RESULTS Median IFN-α (50.1 vs. 34.8 pg/mL, p=0.035), IFN-β (39.1 vs. 23.0 pg/mL, p=0.013), and IFN-γ (26.7 vs. 18.5 pg/mL, p=0.023) levels on the first day post-MI were higher in the AR group compared to the RR group. At 14 days post-MI, IFN levels had decreased in the AR group, while they had not changed in the RR group. At 45 days post-MI, IFN levels were similar between the AR and RR groups. High IFN-α level on the first-day post-MI was an independent predictor of AR (OR: 1.23, 95% CI: 1.06-1.43, p=0.008). CONCLUSION High IFN levels in the acute phase post-MI are associated with AR. Among IFNs, IFN-α is an important predictor of AR. Stable IFN levels appear to be associated with cardiac healing. KEY WORDS Cardiac remodeling, Interferons, Inflammation, Myocardial infarction.