Treatment of all coronary arteries is important to improve the prognosis of acute coronary syndrome after early reperfusion of the culprit lesion. Early statin treatment has been reported to cause regression of plaques away from the site of the culprit lesion in patients with acute coronary syndrome. However, the precise mechanism of coronary plaque regression is not well understood. We studied the effects of statins on the regression of coronary plaques away from the culprit lesions in 120 patients with acute coronary syndrome. We used virtual histology-intravascular ultrasound studies to evaluate nonpercutaneous coronary intervention lesions at admission and short-term (2 to 3 weeks) and medium-term (8 to 10 months) follow-up. According to the medium-term evaluation findings, the subjects were divided into 2 groups: a plaque regression group (n = 94) and a plaque progression group (n = 26). In the regression group, the fibrofatty component had decreased at the short-term (−20.0% vs baseline) and had decreased further at the medium-term (−26.7%) evaluations. The fibrous component had also decreased at the short-term (−5.1%) and medium-term (−8.5%) evaluations. In contrast, the necrotic core component showed a tendency to increase in the short term (+12.5%) but then decreased at the medium-term evaluation (−6.3%). In the progression group, the fibrofatty and fibrous components had increased at the short-term (+37.5%, +11.3%) and medium-term (+50.5%, +13.2%) evaluations; however, the necrotic core had decreased at the short-term (−19.0%) and medium-term (−23.8%) evaluations. In conclusion, regarding the course of coronary plaque regression by statin therapy, the plaques began to reduce the volume of fibrofatty and fibrous components in the early phase, associated with a transiently increased necrotic core component. Furthermore, even in the case of plaque progression, statins caused a reduction in the necrotic core.