Background As a substudy of a large randomized ZEST trial comparing first-and second-generation of drug-eluting stent, we evaluated intimal hyperplasia (IH) and vascular changes using volumetric intravascular ultrasound analysis. Methods Complete angiographic and volumetric IVUS data at immediate post-stenting and 9-month follow-up were available in 162 patients with 183 lesions: 61 in sirolimus-eluting stent group (SES), 64 in paclitaxel-eluting stent group (PES) and 58 in zotarolimus-eluting stent group (ZES). External elastic membrane (EEM), stent, lumen, and peri-stent plaque volumes (EEM minus stent) were normalized by stent length. %IH volume was calculated as [IH volume/stent volume x100, %]. Results Reduction of minimal luminal area (MLA) was more remarkable in PES than SES (-1.4짹1.5mm2 vs. -0.7짹0.9mm2, p=0.002), whereas MLA change in ZES was not significantly different from that in SES (-1.2짹1.0mm2 vs. -0.7짹0.9 mm2, p=0.078). The increase in %IH volume was smaller in SES group compared with PES (9.8짹6.0% vs. 17.5짹11.2%, p<0.001) or with ZES (9.8짹6.0% vs. 18.2짹7.6%, P<0.001). Between ZES and PES, there was no significant difference in changes of %IH volume (17.5짹11.2% vs 18.2짹7.6, p=1.000) or changes of normalized lumen volume (-1.2짹1.3 mm2 vs. -1.1짹0.8 mm2, p=1.000). Late stent malapposition was identified in 8 (13%) in SES, 2 (3%) in PES and no lesion in ZES (p=0.004). Angiographic restenosis was detected in 6 lesions (3 in PES and 3 in ZES). Conclusions The degree of neointimal growth in ZES was similar to PES, and ZES showed lower incidence of late stent malapposition than SES.