Aim To study the distribution of CYP2C19, ABCB1, and PON1 genotypes and their correlation with clopidogrel resistance in patients with coronary heart disease in Tai'an. Methods A total of 594 patients with coronary heart disease who were treated with clopidogrel during hospitalization in Tai'an Central Hospital from January 2019 to March 2020 were selected. Fluorescence in situ hybridization was used to detect CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), ABCB1 (rs1045642) and PON1 (rs662) gene types. Results CYP2C19*2, CYP2C19*3, CYP2C19*17 genotypes in patients with coronary heart disease in Taian were mainly with homozygous (GG). The frequencies of CYP2C19*2 GG, CYP2C19*3 GG, CYP2C19*17 CC, ABCB1 CT and PON1 AG were 48.0%, 89.6%, 97.0%, 46.8% and 47.1% respectively. There was no significant difference in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1, PON1 genotype distribution and allele distribution between male and female patients (P＞0.05). Significant regional differences in the frequency of CYP2C19 alleles and the distribution of metabolic types were found in patients with coronary heart disease in Tai'an. Among 594 patients included in the study, there were 287 patients with a risk level of clopidogrel resistance ≥ 2 in the composite evaluation of patients, approximately 48.3% of the total number of patients. This indicated that clopidogrel resistance was present in 48.3% of patients on the regular dose of clopidogrel. Of the 287 people with a risk level ≥ 2,6 had a normal CYP2C19 metabolic type, representing approximately 7.7% of the total number of patients. Conclusion There were gene polymorphisms observed in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 and PON1 distribution in patients with coronary heart disease in Tai'an, and ABCB1 and PON1 gene polymorphisms would had an impact on the outcome of medication guidance in approximately 7.7%.