Periodontitis is a chronic inflammatory disease and might be a potential risk factor for ischemic heart disease (IHD). However, the link between periodontitis and atherosclerosis is not yet fully understood. Paraoxonase-1 (PON-1) is a new biomarker representing both anti-atherosclerotic and antioxidant activity, which also acts against dental biofilm formation and periodontitis. The possible contributing role of PON-1 in the relationship between periodontitis and atherosclerosis has not been studied to date. The aim of the present study was to investigate the serum level of PON-1 with regard to the periodontal status in IHD patients. In this case-control study, 67 patients with IHD underwent a periodontal examination and were accordingly allocated to one of the 2 study groups: the case group with chronic periodontitis (n = 36); or the control group with a healthy periodontium (n = 31). Serum PON-1 activity was measured by means of colorimetric analysis. There were no significant differences between the groups in terms of demographic data, cardiac risk factors, initial biochemical test results, cardiac pump function, and the number of grafted vessels. The activity of PON-1 in cardiac patients suffering from periodontitis was significantly lower than in cardiac patients with a healthy periodontal status (53.01 ±7.53 U/mL and 59.11 ±9.95 U/mL, respectively; p = 0.007). This finding suggests that the combination of IHD and periodontitis is associated with lower PON-1 activity. Further studies might be required to assess the possible role of periodontal treatment in increasing PON-1 activity and reducing IHD severity.