Background It has been reported that stent deployment results in acute inflammation and platelet deposition as an acute phase reaction and smooth muscle cell (SMC) proliferation as a chronic phase reaction. Other studies have shown that statin therapy can reduce thrombosis as a pleiotropic effect. The present study was undertaken to examine whether preprocedural statin therapy can reduce the thrombotic reaction after stent implantation by using in-stent restenosis (ISR) tissue. Methods and Results The study group consisted of 45 consecutive patients (stable angina) with ISR who underwent directional coronary atherectomy (DCA). According to the histological findings, the patients were divided into 2 groups: those whose ISR tissue included thrombus and SMC (T group), and those whose ISR tissue included only SMC (S group). Just before DCA, serum markers were evaluated, including high-sensitivity C-reactive protein (hs-CRP), lipoprotein (a), plasminogen activator inhibitor-1 (PAI-1), fibrinogen, total cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, and hemoglobin A_1c. Preprocedural medications, including statins, were also evaluated. The values for hs-CRP and PAI-1 in the T group were significantly higher than those in the S group, and the rate of statin use in the T group was significantly lower than that in the S group. There were no significant differences in any of the other factors. Multivariate analysis revealed that preprocedural statin use and the PAI-1 level were significant independent variables affecting the histological findings. Conclusion Preprocedural statins, associated with the involvement of PAI-1, can reduce the thrombotic reaction after stent implantation. (Circ J 2008; 72: 232 - 237)