Abstract Background The detailed mechanism of plaque stabilization by statin therapy is not fully understood. Objectives The aim of this study was to assess the effect of lipid-lowering therapy with 20 mg/day of atorvastatin versus 5 mg/day of atorvastatin on fibrous cap thickness in coronary atherosclerotic plaques by using optical coherence tomography (OCT). Methods Seventy patients with unstable angina pectoris and untreated dyslipidemia were randomized to either 20 mg/day or 5 mg/day of atorvastatin therapy. OCT was performed to assess intermediate nonculprit lesions at baseline and 12-month follow-up. Results Serum low-density lipoprotein cholesterol level was significantly lower during therapy with 20 mg/day compared with 5 mg/day of atorvastatin (69 mg/dl vs. 78 mg/dl; p = 0.039). The increase in fibrous cap thickness was significantly greater with 20 mg/day compared with 5 mg/day of atorvastatin (69% vs. 17%; p < 0.001). The increase in fibrous cap thickness correlated with the decrease in serum levels of low-density lipoprotein cholesterol (R = −0.450; p < 0.001), malondialdehyde-modified low-density lipoprotein (R = −0.283; p = 0.029), high-sensitivity C-reactive protein (R = −0.276; p = 0.033), and matrix metalloproteinase-9 (R = −0.502; p < 0.001), and the decrease in grade of OCT-derived macrophages (R = −0.415; p = 0.003). Conclusions Atorvastatin therapy at 20 mg/day provided a greater increase in fibrous cap thickness in coronary plaques compared with 5 mg/day of atorvastatin. The increase of fibrous cap was associated with the decrease in serum atherogenic lipoproteins and inflammatory biomarkers during atorvastatin therapy. (Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study; NCT00700037 )