The role of an advanced glycation end product/receptor for advanced glycation end product (AGE/RAGE) system in the pathogenesis of coronary artery disease (CAD) is not fully understood. To clarify whether polymorphisms of the RAGE gene were related to CAD, we performed a case-control study in Chinese Han patients. The allele frequencies and genotype distribution combinations of the -429T/C, 1704G/T and G82S polymorphisms of the RAGE gene were compared in 200 cases of hypertension (HT), 155 cases of CAD combined with HT (CAD&HT), 175 cases of CAD and 170 control subjects. Polymerase chain reaction-restriction fragment length polymorphism was used for detection of genotypic variants. The S allele frequency of the G82S polymorphism was higher in the CAD (odds ratio (OR), 2.303, 95% confidence interval (CI) 1.553-3.416; P<0.001, P(corr)<0.003) and CAD&HT (OR, 1.842; 95% CI 1.219-2.785; P<0.003, P(corr)<0.009) groups when compared with the control group. However, the S allele frequency was not significantly different between the CAD and the CAD&HT patient groups (P=0.223), and no statistically significant difference of genotype or allele frequency distributions was observed in the HT group (P>0.05). Meanwhile, serum CRP was significantly associated with the G82S variant. Haplotype-based logistic regression analysis revealed that haplotype G-Ser-T (OR, 1.670; 95% CI, 1.017-2.740; P=0.043), compared with the reference haplotype T-Gly-T, was associated with an increased risk of CAD after adjusting for other risk factors. Further analysis limited to non-diabetic participants exhibited similar significant findings. The haplotype carrying the G82S variant of the RAGE gene was significantly associated with an increased risk of CAD, but not with HT patients. Moreover, a remarkable association of the G82S variant with serum CRP levels implied that the prevalence of RAGE 82S allelic variation might influence susceptibility to CAD by affecting vascular inflammation.