Background:Chronic obstructive pulmonary disease (COPD) affects approximately 400 million people worldwide and is associated with high mortality and morbidity. The effect ofEPHX1andGSTP1gene polymorphisms on COPD risk has not been fully characterized.Objective:To investigate the association ofEPHX1andGSTP1 genepolymorphisms with COPD risk.Methods:A systematic search was conducted on 9 databases to identify studies published in English and Chinese. The analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines (PRISMA). The pooled OR and 95% CI were calculated to evaluate the association ofEPHX1andGSTP1 genepolymorphisms with COPD risk. The I2test, Q test, Egger’s test, and Begg’s test were conducted to determine the level of heterogeneity and publication bias of the included studies.Results:In total, 857 articles were retrieved, among which 59 met the inclusion criteria. TheEPHX1rs1051740 polymorphism (homozygote, heterozygote, dominant, recessives, and allele model) was significantly associated with high risk of COPD risk. Subgroup analysis revealed that theEPHX1rs1051740 polymorphism was significantly associated with COPD risk among Asians (homozygote, heterozygote, dominant, and allele model) and Caucasians (homozygote, dominant, recessives, and allele model). TheEPHX1rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with a low risk of COPD. Subgroup analysis showed that theEPHX1rs2234922 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Asians. TheGSTP1rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk. Subgroup analysis showed that theGSTP1rs1695 polymorphism (homozygote and recessives model) was significantly associated with COPD risk among Caucasians. TheGSTP1rs1138272 polymorphism (heterozygote and dominant model) was significantly associated with COPD risk. Subgroup analysis suggested that theGSTP1rs1138272 polymorphism (heterozygote, dominant, and allele model) was significantly associated with COPD risk among Caucasians.Conclusion:The C allele inEPHX1rs1051740 among Asians and the CC genotype among Caucasians may be risk factors for COPD. However, the GA genotype inEPHX1rs2234922 may be a protective factor against COPD in Asians. The GG genotype inGSTP1rs1695 and the TC genotype inGSTP1rs1138272 may be risk factors for COPD, especially among Caucasians.