Objective: Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality in Korea. And smoking is a well known major contributing factor. Glutathione S-transferase (GST) is implicated in the detoxification of reactive oxygen species (ROS) generated by smoking, and polymorphism of GST gene is suggested as a susceptibility factor to CAD. In this study, we investigated the possible associations between GSTM1/T1 polymorphisms and smoking related CAD development. Subject and Methods: To analyze the effect of GSTM1/T1 gene polymorphisms on the development of smoking related CAD, 415 Korean patients who underwent coronary angiography in Kyung Hee University Hospital Cardiovascular Center were enrolled. The GSTM1 and GSTT1 polymorphisms were analyzed using multiplex polymerase chain reaction (PCR) for GSTM1/T1 genes and CYP1A1 gene for internal control. Result: The genotype frequencies of null GSTM1 and GSTT1 showed no significant differences between CAD group and non-CAD group, respectively. When we analyzed both genotypes, null GSTM1/T1 (both null types) showed significant increase in the risk of CAD (p=0.0003; OR=2.93; 95%CI:1.63-5.26). To study the effect of GST polymorphism on the smoking related CAD development, we also compared the frequencies of GST polymorphisms in smoking(+) CAD group with that in smoking(-) CAD group. The null GSTT1 type was associated with increased risk of developing smoking related CAD (OR=1.65; 95%CI: 0.95-2.83), but this increase was not significant. When we analyzed both genotypes, null GSTM1/T1 (both null types) showed increased risk of smoking related CAD (OR=2.18; 95%CI:0.93-5.09). Conversely, in the non-CAD group, there was no difference of GST genotypes in the smoking and non-smoking group (OR:0.54; 0.19-1.54). Conclusion: This study showed that GST gene polymorphism may influence the development of CAD, especially smoking related CAD.