Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10-20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73-3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.