Background—This study used serial volumetric intravascular ultrasound (IVUS) to evaluate the effect of preinterventional arterial remodeling on in-stent intimal hyperplasia (IH) after implantation of non–polymer-encapsulated paclitaxel-coated stents.Methods and Results—Patients were randomized to placebo or one of two doses of paclitaxel (low dose, 1.28 &mgr;g/mm2; high dose, 3.10 &mgr;g/mm2). Complete preinterventional, post–stent implantation, and follow-up IVUS were available in 18 low-dose and 21 high-dose patients. IH volumes were similar in low-dose and high-dose patients: 17.6±15.1 mm3in low-dose patients and 13.1±13.3 mm3in high-dose patients (P=0.3). Therefore, IVUS findings in low- and high-dose patients were combined. Preinterventional remodeling was assessed by comparing lesion site to proximal and distal reference arterial area: positive remodeling (lesion>proximal reference, n=13), intermediate remodeling (distal reference<lesion<proximal reference, n=13), and negative remodeling (lesion<distal reference, n=13). During follow-up, there was a decrease in lumen volume in positive remodeling lesions (from 106±30 to 90±27 mm3;P=0.0067) and in intermediate remodeling lesions (from 97±28 to 76±31 mm3;P=0.0004), but not in negative remodeling lesions (99±27 versus 92±32 mm3;P=0.15). The follow-up IH volume was lower in negative remodeling lesions (5±7 mm3) compared with positive remodeling (20±14 mm3;P=0.0051) and intermediate remodeling lesions (20±15 mm3;P=0.0043); however, IH volume was virtually identical in positive and intermediate remodeling lesions. Multivariate linear regression analysis determined that remodeling and inflation pressure were independent predictors of IH volume; variables tested in the model included diabetes, acute coronary syndromes, dose, remodeling, and preinterventional plaque burden.Conclusions—Preinterventional arterial remodeling, especially negative remodeling, influences neointimal hyperplasia suppression after implantation of non–polymer-encapsulated paclitaxel-coated stents.