First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5 ± 3.6 vs −4.2 ± 6.9, p < 0.001) and distal (+4.6 ± 7.9 vs −4.8 ± 9.3, p = 0.003) segments. The reference segment did not show any significant difference in vasodilatation between the two groups (+9.8 ± 6.4 vs +7.2 ± 5.2, p = 0.17). Endothelium-dependent vasomotion at adjacent stent segments is relatively preserved after EES implantation while vasoconstriction was observed after PES implantation.