Background: Cyclooxygenase-2 (COX-2) plays a role in the formation of prostaglandins, which contribute to the inflammation involved in atherosclerosis. However, the role of the COX-2 –765G>C polymorphism in susceptibility to coronary artery disease (CAD) is controversial. The objective of the present study was to determine if the COX-2 –765G>C polymorphism predicts risk for coronary artery disease (CAD) in Koreans treated with stents. Methods: Using polymerase chain reaction-restriction fragment length polymorphism, the COX-2 –765G>C polymorphism was analyzed in 622 Korean patients with stents and in 202 healthy control subjects. Results: The GC+CC genotype frequencies of the –765G>C polymorphism were significantly different between the stents and control groups. The COX-2 –765G>C polymorphism showed peculiar associations with CAD according to the presence of hyperlipidemia and plasma folate levels. However, there were no associations between the –765G>C polymorphism and the rates of hypertension, diabetes mellitus, or homocysteine levels. Conclusion: This study suggests that the COX-2 –765G>C polymorphism is a possible genetic determinant for the risk of CAD, and individual risk factor in Koreans. Thus, further association studies between the COX-2 polymorphism and atherosclerotic-related diseases such as cerebrovascular or cardiovascular diseases in other races or ethnicities are recommended.