Clopidogrel resistance is a phenomenon which has clinical implications related to the evolution and unfavorable prognosis of patients with acute coronary syndromes (ACS). Although different mechanisms for Clopidogrel resistance have been suggested, genetic polymorphism of liver enzyme CYP2C19 is on of the most prominent. The aim of the study was to determine variations in response to Clopidogrel in a group of 96 patients diagnosed with acute coronary syndromes (ACS), by genotyping the CYP2C19 cytochrome and the ABCB1 gene. CYP2C19 and ABCB1 polymorphisms were investigated using two methods: TaqMan Assay and High Resolution Melting (HRM) technique. Depending on the genotypic constellation of the alleles studied for CYP2C19 gene, patients were divided into several prediction categories: normal metabolizer (6.25%); intermediate metabolizer (0%); slow metabolizer (17.70%); very fast metabolizer (60.41%) and unpredictable metabolizer (15.62%). HRM technique may be a viable alternative to determine the CYP2C19*2, CYP2C19*17 and ABCB1 polymorphisms, being less expensive than TaqMan Assay.