Background: We reported that thin cap fibroatheroma (TCFA) was an important predictor for vulnerable plaque (VP) in 8-months follow up period. We evaluated to find clinical and intravascular ultrasound-virtual histology (IVUS-VH) predictors for VP in intermediate lesion with recently proposed new lesion classification in 2-years follow up period. Methods: Study subjects consisted of 100 lesions in 96 patients (61.8짹11.7 years old, 69 males) with intermediate coronary artery lesion (stenosed 30%~70%), who underwent IVUS-VH examination. Follow up IVUS-VH were performed in 77 lesions (77%) at mean 8.4짹3.1 months follow-up period and 2-years clinical follow up was done in 96 patients (100%). We defined VP as ACS due to the intermediate lesion or TLR due to rapid lesion progression during follow up period. Results: There were 2 deaths, 3 myocardial infarction, 2 strokes, 15 target lesion revascularization (TLR) in 14 patients during follow up. Patients with TLR were younger (55.5 vs. 62.8years old, p=0.037), larger proximal and distal reference diameter (3.39짹0.72 vs. 2.90짹0.65mm, p=0.009 and 2.96짹0.61 vs. 2.63짹0.56mm, p=0.041, respectively) and higher fibrofatty area (1.52짹1.74mm² vs. 0.84짹1.00mm², p=0.035) than those without TLR in terms of demographic, angiographic, gray scale IVUS and VH-IVUS findings. Thick cap fibroatheroma (FA) was the most common lesion type (n=33), followed by TCFA (n=28), fibrocalcific atheroma (FCA, n=23), pathological intimal thickening (PIT, n=13) and fibrotic atheroma (n=3). TCFA showed highest risk for rapid lesion progression (17.9%), followed by PIT (15.4%), FCA (13.0%) and thick cap FA (9.1%), when we excluded the fibrotic atheroma due to very low incidence (n=3). The risk of rapid lesion progression requiring TLR was increased into 20.0% if patient presenting with MLA<4.0mm² and lesion type of TCFA. Multivariate analysis revealed that the independent predictors for lesion rapid progression was lesion fibrofatty area (beta=0.211, 95% confidence interval 0.005 to 0.126, p=0.035). Conclusion: This study suggests that lesion fibrofatty area is an important reliable predictor for VP in patients with intermediate lesion during 2 years follow up period and lesion type by IVUS-VH and MLA<4.0mm² by gray scale IVUS may not be accurate predictor for predicting plaque vulnerability.