Aims: The aim of this study was to evaluate the effect of low-dose versus high-dose rosuvastatin therapy on the necrotic core (NC) content in coronary plaques of angiographic non-significant lesions as assessed by intravascular ultrasound - virtual histology. Methods and results: Eighty-seven statin-naive patients with ST-segment elevation myocardial infarction (STEMI) were randomised to 5 mg or 40 mg rosuvastatin. The volume of each plaque component (necrotic core, fibrous tissue, fibro-fatty, and dense calcium) was assessed at baseline and after 12 months of follow-up. Baseline low-density lipoprotein (LDL) cholesterol level was reduced by 31.8% in the low-dose group (from 3.1±0.7 mmol/l to 2.0±0.4 mmol/l, p<0.001) vs. 49.0% in the high-dose group (from 3.1±1.0 mmol/l to 1.6±0.7 mmol/l, p<0.001) (p=0.001 between groups). The plaque component necrotic core was reduced by 7.6% in the low-dose group (44.6±38.2 mm 3 vs. 41.2±40.3 mm 3, p=0.29) compared to 14.2% in the high-dose group (47.4±38.2 mm 3 vs. 40.7±34.4 mm 3, p=0.003) (p=0.38 between groups). Conclusions: In statin-naive patients with STEMI, rosuvastatin therapy for 12 months resulted in significant reduction in LDL-cholesterol; however, a significant decrease in necrotic core volume was only seen in the high-dose group. (Clinicaltrials.gov Identifier: NCT01058915).