Objective To investigate the relationships between the cytochrome 2C19 gene (CYP2C19) loss-of-function (LOF) allele with clopidogrel platelet reactivity and cardiovascular end point events in the elderly patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods Over-65-year-old consecutive CHD patients who accepted selective PCI in our department from September 1, 2011 to December 1, 2012 were recruited in this study. They were given clopidogrel loading dose therapy before PCI, and their peripheral blood samples were collected on the day of PCI to detect platelet aggregation. The candidate genetic variants, CYP2C19*2 and *3 LOF alleles, were determined by using SNaPshot assay, and the results were recorded in the clinical data. All patients received maintenance dose of aspirin and clopidogrel during 1 year’s follow-up after PCI, and the major adverse cardiovascular events were observed in this period. Results A total of 436 elderly CHD patients were recruited. Significant difference of platelet reactivity was found between CYP2C19*2 carriers and non-carriers (P＝0.001), but not for CYP2C19*3 (P＝0.884). The patients carrying CYP2C19*2 allele or at least one CYP2C19 LOF allele had significantly higher incidence of cardiovascular end point events than those non-carriers (P＜0.05). Compared with non-carriers, the risk of rehospitalization for angina was significantly higher in the CYP2C19*2 allele carriers [adjusted odds ratio (OR): 1.67, 95% confidence interval (CI): 1.05?2.65, P＝0.010]. What’s more, the risk of combined cardiovascular events (adjusted OR: 1.22, 95% CI: 1.03?1.98, P＝0.049) and the incidence of rehospitalization for angina (adjusted OR: 1.67, 95% CI: 1.04?2.68, P＝0.032) were significantly higher in the CYP2C19 LOF allele carriers than in non-carriers. Conclusion CYP2C19 LOF alleles are closely related to the platelet reactivity of clopidorgrel in the elderly CHD patients after PCI. The genetic variants significantly weakens the effect of antiplatelet therapy of clopidogrel, and thus significantly increases the risk of cardiovascular end point events after PCI.