Objective To explore the relationship between 765G>C, 1195G>A and 1290A>G single nucleotide polymorphisms (SNP) in the promoter region of cyclooxygenase-2 (COX-2) gene and aspirin resistance in the elderly. Methods One hundred and sixty-two elder patients taking aspirin for antithrombotic therapy were selected, platelet aggregation tests were performed, groups were divided according to test findings, and risk factors of aspirin resistance were analysed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to analyse 765G>C, 1195G>A and 1290A>G SNP in the promoter region of COX-2 gene. Results Patients were divided into aspirin sensitive group (n=108) and non-aspirin sensitive group (n=54). Multiple stepwise Logistic regression analysis indicated that hypertension was an independent risk factor of aspirin resistance. There were significant differences in the genotype distribution and allele frequency of -765G>C SNP between two groups (P=0.027, P=0.030). Logistic regression analysis demonstrated that compared with -765GG genotype, OR of aspirin resistance for -765GC genotype was 3.872 (95% CI 1.081-13.870，P=0.038). There were significant differences in genotype distribution of -1195G>A SNP between two groups (P=0.018), and there was no significant difference in allele frequencies of A and G between them (P=0.156). There was no significant difference in genotype distribution of -1290A>G SNP between two groups (P=0.091), and there were significant differences in allele frequencies of A and G between them (P=0.025). The frequency of haplotype CGG of -765G>C, -1195G>A and -1290A>G in non-aspirin sensitive group was significantly higher than that in aspirin sensitive group (P<0.05). Conclusion Haplotype C-G-G of -765G>C, -1195G>A and -1290A>G may be related to aspirin resistance, and -765G>C gene polymorphisms may be genetic risk factor of aspirin resistance for elder patients.