Diffuse-type in-stent restenosis (ISR) is associated with higher rate of restenosis after balloon angioplasty, requiring new therapeutic modalities; therefore, it is clinically important to identify the determinants of diffuse-type ISR. We evaluate the clinical and angiographic variables to predict diffuse-type ISR after coronary stent placement. Two hundred and ten ISR lesions in 196 patients (diffuse ISR, 114 lesions; focal ISR, 96 lesions) were reviewed in this study. Clinical, procedural and quantitative coronary angiographic parameters were analyzed. Diffuse-type ISR was defined as a > or = 50% lumen narrowing and > or = 10-mm length. Univariate analysis revealed that initial lesion length, smaller vessel size, diabetes, multivessel disease, multiple stents, and long stent were significantly associated with diffuse-type ISR. However, diabetes was the only independent predictor of diffuse-type ISR by stepwise multiple regression analysis (OR, 3.3; 95% CI, 1.4-7.4, P = 0.001). Diabetes was associated with diffuse-type ISR after coronary stent placement. It may reflect enhanced rate of neointimal hyperplasia within the stent in diabetic patients.