Background: We compared the effect of arterial remodeling on intimal hyperplasia (IH) after the implantation of a sirolimus-eluting stent (SES) and a paclitaxel-eluting stent (PES). Methods: The study population consisted of patients with positive or intermediate remodeling and negative remodeling. Results: Sixty-nine patients had positive or intermediate remodeling and 107 patients had negative remodeling. At follow-up, late loss was significantly larger (0.58 ± 0.65 vs. 0.38 ± 0.55 mm; p = 0.026) in the patients with positive or intermediate remodeling. The IH volume (22.6 ± 26.2 vs. 12.4 ± 17.4 mm3; p = 0.002) and the percent IH (12.9 ± 14.8 vs. 7.0 ± 9.6%; p = 0.002) were significantly higher in the patients with positive or intermediate remodeling. Compared to negative remodeling, the IH volume was higher in the PES patients with positive or intermediate remodeling, but this difference was not noted in the SES patients. Multiple-regression analysis revealed that arterial remodeling was a significant independent variable for predicting IH volume in the PES patients (p = 0.018). A positive correlation was found between the remodeling index and the IH volume in the PES patients (r = 0.234, p = 0.028), but not in the SES patients. Conclusions: This prospective observational intravascular ultrasound study showed that drug-eluting stents may have a different effect on reducing IH accumulation in lesions with preinterventional positive remodeling characteristics which may be related to the different properties of the drug and delivery platform.