Background: Although the use of drug-eluting stents has significantly reduced the rate of in-stent restenosis (ISR), ISR is still a serious medical problem that needs to be addressed. The main mechanism of ISR has been found to be neointimal hyperplasia, which is related to endothelial dysfunction and vascular inflammation. Recently, small dense LDL (sd-LDL) has emerged as an important risk factor in the development and progression of coronary atherosclerosis and has been associated with endothelial dysfunction and vascular inflammation. Therefore, we investigated whether changes in LDL particle size after percutaneous coronary intervention (PCI) are related to the development of ISR. Methods: A total of 375 stents (Bare metal stent: 262 lesions, Drug eluting stent: 113 lesions) in 249 patients who underwent coronary angiography (CAG) with a stable angina or acute coronary syndrome were enrolled in this study. Blood samples were collected at both the initial and follow-up CAG, and the particle size and fraction of LDL (Quantimetrix LipoprintTM LDL System), high sensitivity C-reactive protein (hsCRP), and lipid profiles were measured. The development of ISR was evaluated at six to nine months after PCI. Results: Follow-up CAG revealed ISR in 78 lesions (21 %). Changes in LDL particle size between the initial and follow-up CAG were 0.32 짹 0.92 nm in the patent stent group and 0.26 짹 1.05 nm in the ISR group (p = 0.015). Logistic multivariate analysis revealed that the stent length (��� 24 mm) (p=0.016, OR=2.117), the increase in LDL size (1st tertile) (p = 0.013, OR = 0.354), post minimal luminal diameter (MLD, ��� 3.0 mm) (p = 0.020, OR = 0.473), and intial hsCRP (2nd and 3rd tertile) (p= 0.009, OR=2.994 and p=0.020, OR=2.692, respectively) were significant predictors of ISR in all lesions. Conclusions: In the present study, a change in LDL particle size between initial and follow-up angiography was associated with ISR, even after adjusting for the LDL level, hsCRP, and angiographic parameters. Therefore, modification of LDL particle size may help prevent ISR in these patients.