Background: Although various predictors relating to ISR have been demonstrated, the relation between the parameters of intravascular ultrasound (IVUS) and inflammatory markers and ISR have not been reported. The aim of this study was to evaluate the predictive factors of in-stent restenosis (ISR) after stent implantation in patients with coronary artery disease. Methods: This study included 120 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a soft plaque group (n=50) and non-soft plaque group (n=70) on the basis of pre-intervention plaque morphology. All patients underwent angiographic and IVUS follow-up at 6 months. Results: The baseline C-reactive protein (CRP) level was significantly higher in the soft plaque group. The follow-up minimal lumen diameter was significantly smaller in the soft plaque group. The pre-intervention remodeling index was significantly higher in the soft plaque group and the positive remodeling was more frequently observed in the soft plaque group. Soft plaques were detected in 70% of the ISR group and, in contrast, in only 30% of the non-ISR group. And ISR was observed in 42% of soft plaque group, in contrast, in only 13% of non-soft plaque group. The neointima area was significantly larger in the soft plaque group (3.7짹1.5mm2 vs. 1.9짹1.5mm2, p<0.001). In non-soft plaque group, association between the baseline CRP level and ISR development was not observed. However, when the analysis was confined to patients with soft plaque, high CRP level was associated with ISR significantly (63% vs. 10%, p<0.001). By multivariate analysis, combination of soft plaque and elevated CRP was the most significant independent predictor of ISR. Conclusions: Measuring pre-interventional plaque morphology and CRP levels may be helpful to predict ISR after stenting.