Methionine synthase (METH, i.e., MTR) is a key enzyme in the folate pathway, which plays a critical role in the synthesis, repair, and methylation of DNA. The association between METH gene polymorphisms and prostate cancer susceptibility remains ambiguous. Thus, we performed an updated meta-analysis of METH single-nucleotide polymorphism rs1805087 involving 12 independent case-control studies comprising 9986 prostate cancer patients and 40134 controls. The odds ratio and 95% confidence intervals were applied to evaluate the relation of this single-nucleotide polymorphism with prostate cancer. Statistical analysis was performed in STATA 11.0. A significant association was found between rs1805087 and increased prostate cancer risk, overall and with Hardy–Weinberg equilibrium. In subgroup analyses (based on ethnicity, source of control, genotyping methods, or publication status), similar associations were observed (e.g., genotype GA vs. AA: odds ratio 1.19, 95% confidence interval 1.01–1.40 among whites; G allele vs. A allele: odds ratio 1.14, 95% confidence interval 1.02–1.28 among hospital-based controls). Thus, the common polymorphism (rs1805087) of METH may be associated with increased prostate cancer risk. Further studies with a larger sample size and detailed gene–environment interactions should be conducted to identify the role of METH polymorphisms in prostate cancer susceptibility.