Background: While statin induces plaque regression, its effects, particularly with different doses on plaque virtual histology composition, remain unknown. Methods and Results: In this prospective, randomized, double-blinded study, 40 consecutive statin-naive patients with stable angina requiring percutaneous coronary intervention (PCI) were randomized to 2 arms (20 patients each) receiving 6 months of atorvastatin 10 mg or 40 mg daily. The primary end-point was (VH-IVUS) changes from baseline to 6 months, as assessed by a core laboratory. Fifty-four VH-IVUS lesions were analyzed from the 10 mg group and 57 from the 40 mg group. Overall, plaque volume was reduced by 4.28% (-5.10 +/- 14.93 mm(3), P<0.001), absolute VH-IVUS fibrous volume by 10.54% (-4.87 +/- 10.74 mm(3), P<0.001), and relative percentage fibrous component by 3.29 +/- 7.84% (P<0.001), while relative percentage dense calcium increased by 1.50 +/- 3.08% (P<0.001), and necrotic core by 3.19 +/- 7.82% (P<0.001). Beneficial changes were more substantial in the higher dose (40 mg) group, with significantly more percentage plaque volume regression (-1.50 +/- 3.85% vs. 0.38 +/- 4.05% increase in the 10 mg group, P=0.014), less relative percentage necrotic core expansion (1.68 +/- 7.57% vs. 4.78 +/- 7.82% in the 10 mg group, P=0.037), and without occurrence of major adverse cardiac events (vs. 6 patients in the 10 mg group, P=0.020). Conclusions: In statin-naive patients requiring PCI, 6 months of atorvastatin induced a significant percentage of plaque volume reduction and substantial modification of VH-IVUS composition. In addition, these effects appeared to vary with different doses of atorvastatin, showing significantly better limitation of relative percentage necrotic core expansion at a higher dose. (Circ J 2012; 76: 2662-2672)