Coronary in-stent restenosis represents a clinical problem. Because homocysteine is being discussed as a new risk factor for atherosclerosis and thrombosis, this study investigated the relations of homocysteine, folate, and vitamin B(12) to the rate of in-stent restenosis. Patients undergoing successful percutaneous transluminal coronary angioplasty of native coronary lesions with stent implantation were investigated for fasting total serum homocysteine, folic acid, and vitamin B(12). The rate of in-stent restenosis was determined angiographically after 6 months, or earlier if clinically indicated. Of 292 enrolled patients, 262 (90%) (189 men and 73 women) underwent control angiography on an average of 6.3 +/- 1.0 (SD) months after intervention. The rate of in-stent restenosis was 36%. Univariate and multivariate analyses revealed no significant differences between patients with or without restenosis with regard to total homocysteine (median [interquartile range]: 12.9 [11.2 to 14.8] and 12.4 [10.3 to 15.4] micromol/L, respectively), folate (16.1 [12.4 to 20.5] and 15.4 [12.5 to 19.5] nmol/L, respectively), or vitamin B(12) (239.0 [182.5 to 322.1] and 258.4 [205.8 to 330.5] pmol/L, respectively). These results suggest that homocysteine, folate, and vitamin B(12) are not related to the angiographically determined rate of coronary in-stent restenosis after 6 months.