BACKGROUND AND OBJECTIVES: This study aimed to assess the effect of simvastatin therapy on plaque regression and vascular remodeling in peristent reference segments of normocholesterolemic patients by using serial intravascular ultrasound (IVUS) observation. SUBJECTS AND METHODS: We retrospectively evaluated the poststenting and follow-up IVUS findings in 208 peristent (bare metal stent) reference segments of 108 normocholesterolemic patients (20 mg/day simvastatin group; n=62 vs. non-simvastatin group; n=46); 100 segments were proximal and 108 segments were distal to the stent. Quantitative volumetric IVUS analysis was performed for 5-mm vessel segments immediately proximal and distal to the stent. RESULTS: Follow-up IVUS was performed at a mean of 8.7 months after stenting (range: 3-19 months). For the proximal edge, a significant decrease in the mean lumen area and mean external elastic membrane (EEM) area and a significant increase in the mean plaque and media (P&M) area were observed at follow-up in both simvastatin and non-simvastatin groups. However, the changes in EEM (simvastatin: -0.4+/-0.3 mm2 vs. non-simvastatin: -0.4+/-0.4 mm2, p=0.983), lumen (simva-statin: -0.7+/-0.3 mm2 vs. non-simvastatin: -1.0+/-0.5 mm2, p=0.114), and P&M area (simvastatin: 0.3+/-0.2 mm2 vs. non-simvastatin: 0.6+/-0.4 mm2, p=0.110) from poststenting to follow-up at the proximal edge were not significantly different between the 2 groups. For the distal edge, a significant decrease in the mean lumen area and a significant increase in the mean P&M area were observed at follow-up in both the groups. However, the changes in the EEM area (simvastatin: -0.1+/-0.2 mm2 vs. non-simvastatin: -0.2+/-0.3 mm2, p=0.674), lumen area (simvastatin: -0.6+/-0.2 mm2 vs. non-simvastatin: -1.0+/-0.4 mm2, p=0.087), and P&M area (simvastatin: 0.5+/-0.2 mm2 vs. non-simvastatin: 0.8+/-0.3 mm2, p=0.102) from poststenting to follow-up at the distal edge were not significantly different between the groups. CONCLUSION: A conventional dose of simvastatin does not inhibit plaque progression and lumen loss in the peristent reference segments of normocholesterolemic patients who have undergone bare-metal stent implantation.