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Introduction: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use. Aim: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption (ABCB1) and activation (CYP2C19*2 and CYP2C19*3) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity. Material and methods: This single-center, open-label, prospective study included 199 patients hospitalized due to ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) in Killip class I-III, who underwent percutaneous coronary intervention. The control group included 22 patients with stable coronary artery disease. Results: The mean (SD) levels of active clopidogrel were 17.1 (12.3) ng/ml in controls and 16.4 (12.0) ng/ml in the whole study group (p < 0.68). No differences were noted in clopidogrel levels between patients with STEMI and NSTEMI (mean (SD), 17.6 (2.3) ng/ml and 15.1 (11.5) ng/ml; p < 0.45) or between STEMI and NSTEMI groups and controls (p < 0.38 and p < 0.61, respectively). No effect of ABCB1 or CYP2C19 polymorphism was observed in the study subgroups. Conclusions: We concluded that ACS does not affect the levels of clopidogrel active metabolite or platelet inhibition in patients in Killip class I-III with or without CYP2C19 or ABCB1 gene polymorphisms. [ABSTRACT FROM AUTHOR]