Objective To systematically review the association between prothrombin gene G20210A mutation and the risk of cerebral venous thrombosis (CVT). Methods Databases including PubMed, Springer, Google Scholar, The Cochrane Library (Issue 1, 2016), CNKI, WanFang Data and CBM were searched for case-control studies concerning the association between prothrombin gene G20210A mutation and cerebral venous thrombosis risk from inception to January 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software and Stata 12.0 software. Results A total of 26 case-control studies were included, involving 1 361 CVT cases and 6 323 controls. The results of meta-analysis showed that: there was a significant association between prothrombin gene G20210A mutation and CVT risk (OR=4.56, 95% CI 3.51 to 5.93,P<0.000 01). Sensitivity analysis showed no significant publication bias was detected confirmed the stability of results. Subgroup analysis showed that G20210A mutation increased CVT risk in adults (OR=5.02, 95% CI 3.81 to 6.60,P<0.000 01), but not in children (OR=1.99, 95% CI 0.83 to 4.79,P=0.12). Conclusion Prothrombin gene G20210A mutation can significantly increase the CVT risk. Due to the limited quality and quantity of included studies, the above results are needed to be validated by more high quality studies.