Introduction:There is a well-documented association between coronary artery disease (CHD) and periodontal disease (PD) mediated by common inflammatory pathways. This association, however, has not been investigated extensively in the special context of in-stent restenosis. This study aimed to investigate the periodontal status of patients undergoing percutaneous coronary intervention (PCI) for restenotic lesions.Methods and Results: We enrolled 90 patients undergoing percutaneous coronary intervention and 90 age- and gender-matched healthy controls in the present study. All subjects received a full-mouth examination by a periodontist. Plaque index, periodontal status, and tooth loss were determined. The periodontal state was significantly worse (p< 0.0001) in the PCI group, and each periodontal stage increased the odds of belonging to the PCI group. This effect of PD was independent of diabetes mellitus, another strong risk factor for CAD. The PCI group was further divided into two subgroups: PCI for restenotic lesions (n= 39) and PCI for de novo lesions (n= 51). Baseline clinical and procedural characteristics were comparable between the two PCI subgroups. A significant (p< 0.001) association was found between the PCI subgroup and the severity of periodontal disease, with the incidence of severe PD reaching 64.1%.Conclusions:Patients undergoing PCI for in-stent restenosis exhibit more severe forms of periodontal disease not only as compared to healthy controls but also as compared to patients stented for de novo lesions. The potential causality between PD and restenosis must be studied in larger prospective studies.