We performed a systematic review and meta-analysis with the aim of assessing the association between cytokine gene polymorphisms and graft rejection in heart transplantation. We identified relevant studies from Medline and Embase using PubMed and Ovid search engines, respectively. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Four to 5 studies were included in pooling of 3 gene polymorphisms. The prevalences of the minor alleles for TNF α -308, TGF β 1-c10, and TGF β 1-c25 were 0.166 (95% CI: 0.129, 0.203), 0.413 (95% CI: 0.363, 0.462), and 0.082 (95% CI: 0.054, 0.111) in the control groups, respectively. Carrying the A allele for the TNF α -308 had 18% (95% CI of OR: 0.46, 3.01) increased risk, but this was not significant for developing graft rejection than the G allele. Conversely, carrying the minor alleles for both TGF β 1-c10 and c25 had nonsignificantly lower odds of graft rejection than major alleles, with the pooled ORs of 0.87 (95% CI: 0.65, 1.18) and 0.70 (95% CI: 0.40, 1.23), respectively. There was no evidence of publication bias for all poolings. An updated meta-analysis is required when more studies are published to increase the power of detection for the association between these polymorphisms and allograft rejection.