Objective Circulating microRNAs (miRNAs) are recognized as useful cardiovascular biomarkers in acute coronary syndrome (ACS). Vessel occlusion is not always manifested with ST-elevation; no specific biomarkers have been identified to differentiate ACS with patent or occluded infarct-related coronary artery (IRA). Methods Forty-four consecutive patients (mean age 57.5±9.9 years) with uncomplicated ACS and positive test for myocardial necrosis were admitted. Patients were classified into 2 groups with respect to TIMI flow grading on occluded IRA (patent vs. occluded), and with respect to ST-elevation (STEMI vs. NSTEMI). Standard blood tests and inflammatory markers (hs-CRP, fibrinogen, TNF-α and IL-6) were assayed. Expression levels of selected serum miRNAs (miR-1, -16, -34a, -122, -124, -208b, 133a/b, -375, and -499) were analyzed. Results Sixteen patients were categorized to the patent and 28 to the occluded groups; consistently, 17 STEMI and 27 NSTEMI patients were classified. No demographic differences between STEMI vs. NSTEMI and patent vs. occluded patients were found. STEMI patients had significantly higher troponin T levels but no significant differences with regard to TNFa, hs-CRP were found. In the STEMI group lower fibrinogen concentrations (3.4±1.24 vs. 4.4±1.78 g/L; p=0.049) and a trend to difference in IL-6 levels (9.2±6.62 vs. 5.7±5.43 pg/mL; p=0.073) were observed. Additionally, miR-134 expression was 3.83 fold higher in STEMI vs NSTEMI (p < 0.05).Patients with the occluded IRA had significantly higher levels of circulating miR-133a (fold change: 7.00), miR-133b (4.57), miR-34a (5.50), miR-124 (2.55) and miR-134 (3.45). Conclusions The degree of target vessel occlusion determines circulating miRNA expression. Patent artery produces less circulating brain and cardiac related miRs. It demonstrates distinct pathomechanism of cell damage during MI related ischemia.