The use of drug-eluting stent (DES) has been associated with incomplete endothelialization and coronary endothelial dysfunction. However, the relationship between endothelial vasomotor function and strut coverage evaluated by optical coherence tomography (OCT) has not been sufficiently assessed. Therefore, we evaluated the relationship between endothelial vasomotor function and the degree of stent strut coverage after DES implantation. Coronary angiography and OCT were performed in 112 patients at the 6-month follow-up after DES implantation. The patients were divided into tertiles according to the degree of strut coverage as was assessed by OCT. Endothelial vasomotor function was evaluated with intracoronary infusion of incremental doses of acetylcholine (Ach; 10⁻⁸–10⁻⁶ mol/L). Vascular responses at the proximal and distal segments to the stent margin were evaluated by quantitative coronary angiography analysis before and after Ach infusion. The percentage of uncovered struts in tertiles 1–3 was 4.2 ± 3.3, 17.3 ± 4.2 and 44.5 ± 14.4 %, respectively, (p < 0.001). The percentage of maximal vasoconstriction in tertiles 1–3 was 8.3, 9.1 and 8.1 % at proximal segment to the stent margin (p = 0.95), respectively, and 13.9, 11.1 and 14.2 % at distal segment to the stent margin (p = 0.74), respectively. The percentage of uncovered struts was not correlated with the degree of vasomotor function (r = −0.01, p = 0.92 at the proximal segment; r = −0.07, p = 0.47 at the distal segment). The percentage of strut coverage was not associated with the degree of abnormal vasoconstriction in response to intracoronary infusion of Ach 6 months after DES implantation.