Implantation of a paclitaxel- or sirolimus-eluting stent (SES) may be associated with endothelial dysfunction. In the present study, we compared coronary endothelial function after zotarolimus-eluting stent (ZES) implantation to that after SES implantation. Patients who had one stent implantation for a single lesion in the left anterior descending artery were enrolled. After 6 to 9 months, coronary endothelial function was assessed in patients who showed no angiographic restenosis. Endothelium-dependent vasomotion was determined after intracoronary infusion of acetylcholine. Also, endothelium-independent vasomotion was assessed after nitrate infusion. A total of 23 patients (11 in the ZES group, 12 in the SES group) were included. In distal and far distal segments, the SES group showed significant vasoconstriction by acetylcholine. However, no significant vasomotion was observed in the ZES group (SES versus ZES: -36.1% versus -3.3% for distal; P = 0.003, -34.7% versus -3.4% for far distal; P = 0.003). Endothelium-independent vasodilatation by nitrates was preserved in all subjects. SES implantation may induce significant impairment of the endothelium-dependent vasomotor function in the distal portion of the treated vessel, while ZES implantation may not. Our results suggest that the change in coronary endothelial function after stent implantation could be different according to the type of DES.