Objective To investigate the CYP2C19 polymorphism in the patients with coronary heart disease (CHD) in the central and southern Jiangsu province of China and to compare its distribution in different geographical populations, so as to provide guidance for the rational use of drugs in CHD patients. Methods A total of 2926 patients with coronary heart disease who were admitted to Clinical Medical College of Yangzhou University and First Affiliated Hospital of Soochow University from August 2019 to December 2022, and have completed CYP2C19 gene polymorphism detection, were selected as the study objects. The CYP2C19 gene loci were sequenced by pyrosequencer, and its polymorphism distribution in different regions was compared. SPSS statistics 26.0 was used for data analysis. According to the data type, t test or χ² test was used for comparison between groups. Results A total of 2 926 patients were enrolled in this study. According to the genotype, they were divided into three groups:extensive metabolizer (*1/*1), intermediate metabolizer (*1/*2, *1/*3), and poor metabolizer (*2/*2, *3 and *3), with a frequency of 38.21% (1118/2926), 45.80% (1340/2 926), and 15.99% (468/2 926), respectively. There was no statistically significant difference in the distribution of CYP2C19 alleles and genotypes between male and female CHD patients (P>0.05). The distribution of CYP2C19 allele in CHD patients in central and southern Jiangsu Province was significantly different from that in Shaanxi Province (P<0.05). There was statistical significance in the distribution of CYP2C19 metabolic types in CHD patients in central and southern Jiangsu Province compared with Shaanxi, Guangzhou, Huaihai and Henan regions (P<0.05).Conclusion There are differences in the distribution of CYP2C19 gene polymorphisms in CHD patients in the central and southern of Jiangsu, mainly with the medium and fast metabolic type, and there is no significant difference between genders, which can help the precise medication for the patients with coronary heart disease.