Background—The aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effect of a paclitaxel coating on in-stent intimal hyperplasia (IH).Methods and Results—Patients were randomized to placebo (bare metal stents) or 1 of 2 doses of paclitaxel (low dose: 1.28 &mgr;g/mm2; high dose: 3.10 &mgr;g/mm2). Complete post-stent implantation and follow-up IVUS were available in 81 patients, including 25 control patients and in 28 receiving a low-dose and 28 receiving a high dose. Volumetric analysis of the stented segment and of both reference segments was performed. Baseline stent measurements and both reference measurements were similar among the groups. With increasing doses, there was a stepwise reduction in IH accumulation within the stented segment (31±22 mm3in control, 18±15 mm3in low dose, and 13±14 mm3in high dose,P<0.001). Post hoc analysis showed less IH accumulation when low- and high-dose patients were compared with control (P=0.009 andP<0.001, respectively), but not when low-dose patients were compared with high-dose patients (P=0.2). Focal late malapposition was seen in 1 high-dose patient. With increasing doses, there was no significant change in the reference segments.Conclusions—Paclitaxel-coated stents are effective in reducing in-stent neointimal tissue proliferation in humans. They are not associated with edge restenosis or significant late malapposition.