Aims: In this study, we aimed to investigate whether serum S100A8, S100A9 and S100A12 levels were markers of acute coronary syndrome (ACS). Materials & methods: Patients who underwent coronary angiography and/or percutaneous coronary interventions between June 2015-October 2015 were consecutively recruited in this study and categorized three groups each containing 30 patients (normal coronary arteries, stable coronary artery disease, and acute coronary syndrome). Baseline characteristics, including co-morbidities and medications, were recorded and serum S100A8, S100A9, S100A12, and C-reactive protein levels were measured besides routine laboratory tests. Results: A total of 90 patients (63.00 [56.00-73.00] years, 62.89% male) have been included. None of the groups differed from each other regarding baseline characteristics (p > 0.05). S100A9 levels were elevated in ACS when compared with the normal coronary arteries (p = 0.033) and S100A12 levels were found to be elevated in ACS when compared with both patients with normal coronary arteries and stable coronary artery disease (p = 0.001). S100A12 was identified as an independent associate of ACS (p = 0.002). Conclusion: These results suggest that S100A12 may serve as a marker of coronary plaque instability, and may have a therapeutic implication in ACS treatment.