To assess the association of single nucleotide polymorphisms (SNPs) of endotheline receptor gene with the severity of coronary heart disease (CHD). A total of 553 CHD patients, including 324 patients with mult-vessel disease based on result of selected coronary angiography, and 553 age- and sex-frequency matched controls were selected. Clinical data were collected. Genotypes of rs501120, rs899997, rs1878406 and rs7173743 were determined with TaqMan-MGB probes. The distribution of genotypes of the 4 SNPs showed no significant difference between the two groups. However, the frequency of A allele of rs501120 and T allele of rs1878406 were significantly higher in the CHD group compared with the control group (P< 0.05). For rs7173743 and rs899997, no significant difference was detected between the two groups. After adjusting for conventional risk factors by logistic regression analysis, the results suggested that the distribution of rs1878406 TT+TC genotype in severe multi-vessel disease group is significantly higher than that in the control group (OR=1.43, 95% CI: 1.05-2.07, P=0.033). The above results suggested that the rs1878406 polymorphism of endotheline receptor gene may serve as a genetic marker for severe multi-vessel disease in CHD among ethnic Han Chinese.