The aim of the study was to compare the clinical efficacy and safety of ticagrelor and clopidogrel in patients with coronary heart disease one year after percutaneous coronary intervention (PCI), and to explore their association with the CYP2C19 gene polymorphism. A total of 971 patients with coronary heart disease who were hospitalized and underwent PCI from April 2016 to May 2017 were studied. All 971 patients were divided into three subgroups according to CYP2C19 gene types as fast metabolizing, slow metabolizing and very slow metabolizing type. Patients were also classified according to the oral antiplatelet aggregation drugs they received: clopidogrel group and ticagrelor group. The incidence of major adverse cardiac events (MACE) and bleeding events in the clopidogrel-treated and ticagrelor-treated groups and in patients with fast, slow, and very slow CYP2C19 metabolisms were compared. Binary logistic regression analysis was carried out to analyze the risk factors associated with MACEs and hemorrhagic events. Patients on ticagrelor had a greater number of bleeding complications compared to those on clopidogrel (P<0.001), with no difference in MACE between the two groups (P=0.399). The incidence of MACE was significantly higher in very slow metabolizing patients receiving clopidogrel (P<0.001) while the incidence of bleeding complications was significantly higher in fast metabolizing patients receiving ticagrelor (P<0.001). The regression analysis revealed that the CYP2C19 gene mutation, a dual-antiplatelet therapy, and a stroke history were all significantly associated with MACE. By contrast, a dual-antiplatelet therapy and a stroke history were significantly associated with bleeding events. Findings of the present study indicated that clopidogrel and ticagrelor were equally efficacious post-PCI. Efficacy of clopidogrel was reduced in patients with very slow CYP2C19 genotype while bleeding complications were higher in patients with fast CYP2C19 genotype receiving ticagrelor. CYP2C19 genotyping may be used to provide guidance to optimize individual antiplatelet treatment.