Intimal proliferation is a main cause of in-stent restenosis. Over-excretion of angiotensin I converting enzyme (ACE) and aldosterone is reported to stimulate intimal hyperplasia and the genetic effect of these molecules may alter the process of in-stent restenosis. We hypothesized that the genetic polymorphisms that alter the expression of genes such as ACE I/D, CYP11B2-344C/T, and AGT M235T can affect in-stent restenosis. We analyzed the angiographic and clinical data of 238 patients (272 stents) who underwent coronary stenting and follow-up angiography, and analyzed the genotypes of ACE I/D, CYP11B2-344T/C, and AGT M235T. There was no significant difference in age, sex, or lipid profiles between the patent and restenosis groups. Diabetes mellitus was more frequent in the binary restenosis group. Quantitative computer-assisted angiographic (QCA) analysis revealed that the risk of in-stent restenosis increased with lesion length and was inversely proportional to post-stenting minimal luminal diameter (MLD) and reference diameter. There was no difference in the frequency of binary restenosis between genotypes in each of the three genes. However, follow-up MLD was significantly smaller in the ACE DD genotype than in the ACE II or ID genotypes. Defining restenosis as MLD 2 mm, the restenosis rate was significantly higher in the ACE DD genotype than in the ACE II or ID genotypes. There was no significant synergistic effect between the three gene polymorphisms. In conclusion, while the ACE I/D polymor phism promoted the progress of in-stent restenosis and was of clinical significance, the other potential variables examined did not correlate with in-stent restenosis.