The aim of this meta-analysis was to assess the methionine synthase reductase (MTRR) gene 66A>G polymorphism and male infertility susceptibility. Studies were identified in PubMed and Embase databases. An odds ratio (OR) was used to assess the relationship between MTRR 66A>G polymorphism and male infertility risk. A total of seven case-control studies containing 1438 patients and 1363 controls were enrolled in the meta-analysis. Our results showed that no association exists between the MTRR 66A>G polymorphism and male infertility risk in the total population (GG vs. AA: OR = 1.29, 95% confidence interval [CI] = 1.00-1.66; GA vs. AA: OR = 1.09, 95% CI = 0.92-1.30; dominant model: OR = 1.13, 95% CI = 0.96-1.34; recessive model: OR = 0.83, 95% CI = 0.67-1.03). In a subgroup analysis by nationality, the 66A>G polymorphism was not associated with male infertility in both Asians and Caucasians. In a subgroup analysis stratified by male infertility type, significant association was found with oligoasthenozoospermia (OAT) (GG vs. AA: OR = 1.83, 95% CI = 1.24-269; GA vs. AA: OR = 1.36, 95% CI = 0.88-2.11; dominant model: OR = 1.51, 95% CI = 1.13-2.01; recessive model: OR = 0.62, 95% CI = 0.46-0.85). In summary, the present meta-analysis suggests that MTRR 66A>G polymorphism may be associated with OAT risk.