Paraoxonase-1 (PON1) is an enzyme associated with HDL in blood and it is considered as an anti-oxidant factor due to its capability to prevent lipid oxidation. In vivo mouse studies also have shown that PON1 is one of the genetic risk factors contributing to atherosclerosis. In this study, we evaluated the serum PON1 activities of sex-age matched Korean healthy control and ischemic stroke patients, and investigated the association of PON1 activity with other metabolic parameters. Statistical analyses revealed that PON1 activity and HDL_cholesterol (HDL_C) in stroke patients were significantly decreased when compared with those of healthy control. Additionally, PON1 activity was negatively correlated with age, whereas it was positively correlated with HDL_C in a stroke group. Overall, the results of this study indicated that decreased serum PON1 activity should be considered as a risk factor for ischemic stroke in Koreans.