Background: Several studies have examined the association between transforming growth factor-beta (TGF-beta) genetic polymorphisms and chronic obstructive pulmonary disease (COPD) risk, but the results remained inconclusive and controversial. Aims: We aimed to examine the correlation between TGF-beta genetic polymorphisms and COPD risk through a comprehensive meta-analysis. Additionally, changes in circulating TGF-beta concentrations across genotypes of TGF-beta genetic polymorphisms were analyzed. Methods: Literature search, quality assessment, and data extraction were completed independently and in duplicate. Data are expressed in odds ratio (OR) or weighted mean difference (WMD) with 95% confidence interval (CI). Results: A total of 12 articles, involving 14 independent studies and 7 170 participants, were meta-analyzed for the correlation of five polymorphisms (rs2241712, rs1800469, rs1982073, rs6957, and rs2241718) in TGF-beta gene with COPD risk. Under the allele model, no statistical significance was observed for all polymorphisms associated with COPD risk. Subsidiary analyses indicated that country, COPD stage, and diagnosis of COPD were potential sources of between-study heterogeneity. Filled full plots revealed no missing studies for all studied polymorphisms, except rs1982073. Genotype-phenotype analyses showed that carriers of rs1800469 CT genotype had significantly higher concentrations of circulating TGF-beta than those with CC genotype in COPD patients (WMD: 0.28 pg/ml, 95% CI: 0.01 to 0.56). Conclusion: Our findings failed to support the candidacy of TGF-beta gene in the development of COPD, whereas the contribution of TGF-beta gene to COPD might be ethnicity- and stage-dependent.