Vitiligo is a common pigmentary skin disorder and genetic factors were acknowledged to be greatly associated with the pathogenesis of this disease. Recently, increasing studies investigated the associations of methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms with risks of vitiligo, but the results still remained controversial. The current meta-analysis was conducted to further evaluate the association of MTHFR polymorphisms with risk of vitiligo. Eligible studies were searched in PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP) and Wan Fang Database until October 2020. All analyses were carried out using the Review Manager 5.3 software. A total of 6 studies that involved MTHFR rs1801131 and/or rs1801133 polymorphism were finally included, which enrolled 3599 participants. Our results showed that no correlations were found between MTHFR rs1801131, rs1801133 polymorphisms and vitiligo risks in overall group. However, subgroup analysis revealed that rs1801131 polymorphism was significantly associated with increased vitiligo risk in the allelic (C vs. A: OR=1.15, 95% CI=1.02-1.29, P=0.02) and homozygous models (CC vs. AA: OR=1.48, 95% CI=1.10-2.01, P=0.01) in Asian population and that the rs1801133 polymorphism was significantly associated with decreased vitiligo risk in the allelic model (T vs. C: OR=0.82, 95% CI=0.74-0.92, P=0.0005) also in Asian population. This meta-analysis confirmed the associations of MTHFR rs1801131 and rs1801133 polymorphisms with vitiligo risks and provided comprehensive insight into the pathogenesis of vitiligo. This article is protected by copyright. All rights reserved.