Objective To investigate the role of thromboelastography (TEG) in predicting cytochrome P450 2C19 (CYP2C19) genotype and its value in guiding clopidogrel treatment following percutaneous coronary intervention (PCI). Methods From January 2012 to August 2012, 70 patients with coronary artery disease undergoing PCI were enrolled and treated with aspirin and clopidogrel. They were divided into clopidogrel resistance (CR) group and clopidogrel sensitive (CS) group according to adenosine diphosphate (ADP)-induced platelet aggregation inhibition rate. Genotyping of CYP2C19 in the 70 patients was classified as: extensive metabolizers(*1/*1), intermediate metabolizers(*1/*2, *1/*3) and poor metabolizers(*2/*2, *2/*3, *3/*3). The clinical data, biochemical parameters, and CYP2C19 genotypes were compared between two groups. The independent risk factors of CR were analyzed by multiple logistic regression analysis. A receiver operating characteristic (ROC) curve was used to evaluate the efficacy of ADP-induced platelet aggregation inhibition rate in predicting the genotype of CYP2C19. Results High-density lipoprotein and genotypes of CYP2C19 were significantly different between the CR group (n=31) and CS group (n=39)(P<0.05). Stepwise forward multiple logistic regression analysis found that CYP2C19 poor metabolizers and lower HDL level were independent risk factors for CR (P<0.05). The results of ROC curve demonstrated a satisfactory predictive value for ADP-induced platelet aggregation inhibition rate, with the area under the curve (AUC) being 0.847 (95% CI: 0.729-0.965,P=0.003). When the ADP-induced platelet aggregation inhibition rate was at the optimal cut-off value (39.45%), the sensitivity, specificity, positive predictive value and negative predictive value in diagnosing the poor metabolizers of CYP2C19 were 85.7%, 77.8%, 30% and 98%, respectively. Conclusion CYP2C19 poor metabolizers and lower HDL level are selected as the independent risk factors of CR. When the ADP-induced platelet aggregation inhibition rate is lower than 39.45%, the genotypes of CYP2C19 should be detected to adjust the treatment.