Background Using serial volumetric intravascular ultrasound (IVUS) analyses we evaluated the frequencies and predictors of late intimal hyperplasia (IH) increases after drug-eluting stent (DES) implantation. Methods All eligible patients who underwent 6-month angiography without visual restenosis after DES implantation were requested for 2-year follow-up. Complete serial (post-stenting, early ���6-month,��� and late ���2-year��� follow-up) angiographic and volumetric IVUS data were available in 135 patients with 143 lesions: 99 sirolimus-eluting stents (SES) and 44 paclitaxel-eluting stents (PES). 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 The early reduction in minimum lumen area (MLA) was greater than the late reduction in MLA (-0.8짹0.8 mm2 vs. -0.2짹0.5 mm2, p<0.001). There was a progressive increase in %IH volume: 8.1짹7.1% from baseline to 6 months and 2.4짹3.9% from 6 months to 2 years (p<0.001, comparing early to late increases in %IH volume). PES was the only independent predictor for %IH volume at 6 months (��=0.419, p<0.001). PES (0.365, p<0.001, 95% CI=3.7-9.7) and post-stenting normalized plaque&media volume (��=0.195, p=0.020, 95% CI=0.1-1.6) were the only independent predictors for % IH volume at 2 years. Overall, 4 (3.0%) died from non-cardiac causes; and 1 (0.7%) from sudden death. Stent thrombosis occurred in 1 (0.7%) patient, and acute myocardial infarction in 2 (1.5%) patients. Target vessel revascularization was necessary in 10 (7.4%) patients. Conclusions Although IH continued to increase beyond 6 months after DES implantation, the rate of intimal growth and luminal loss attenuated over time.