Objectives: We hypothesized that higher inflammatory reaction at the culprit lesion may have higher restenosis. We compared plaque composition between patients with instent restenosis (ISR) and those without ISR. Methods: Study population consisted of 241 patients with coronary artery disease, who underwent percutaneous coronary intervention with intravascular ultrasound-virtual histology (IVUS-VH) and 9 months follow up coronary angiography. Results: Patients with ISR (n=27, 8.2%) were likely to be older, increased high sensitivity C-reactive protein (hs-CRP), higher percent fibrofatty volume and higher chance of fibrocalcific and fibrous cap atheroma than those without ISR. The independent predictors for ISR were hs-CRP (beta=0.255, 95% confidence interval (CI); 0.028~0.082, P<0.001), % necrotic core volume (beta=-0.168, 95% CI; -0.010~-0.001, P=0.008) and age (beta=0.158, 95% CI; 0.001~0.008, P=0.015). Subgroup analysis showed that there was no significant independent predictor in patients with stable angina, whereas elevated hs-CRP and % fibrofatty volume were the independent predictors for ISR in patients with acute coronary syndrome. Conclusions: This study suggests that ISR may be associated with plaque composition as well as age and inflammation, although the association between plaque composition and ISR needs to be disclosed.