Background Previous results regarding the prevalence of Factor V Leiden (FVL) in patients with cerebral venous thrombosis (CVT) varied remarkably. Therefore, we performed a meta-analysis to evaluate the potential association between FVL and CVT. Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for relevant case-control studies. The data were pooled for analysis of the association between FVL and CVT with a random-effects model. Subgroup and sensitivity analyses were performed to evaluate the robustness of the results. Publication bias was assessed by funnel plot and the Egger's test. Results A total of 39 case-control studies including 1807 cases of CVT and 7699 control cases were included. FVL was more common in patients with CVT (195/1822) than in controls(369/7795), [odds ratio(OR) = 2.70, 95% confidence interval(CI) 2.16 +/- 3.38, P < 0.00001]. Results of subgroup analyses indicated that the association between FVL and CVT varied according to geographic regions. The associations between FVL and CVT were significant in studies from Germany (OR = 2.42, 95% CI 1.70 +/- 3.45, P < 0.00001), Brazil (OR = 2.82, 95% CI 1.24 +/- 6.42, P = 0.01), France (OR = 5.44, 95% CI 1.35 +/- 21.92, P = 0.02), Iran (OR = 6.61, 95% CI 1.83 +/- 23.93, P = 0.004), and Tunisia (OR = 6.54, 95% CI 2.89 +/- 14.82, P < 0.00001), but not in those from Italy (OR = 1.49, 95% CI 0.59 +/- 3.78, P = 0.40) or the US (OR = 2.37, 95% CI 0.59 +/- 9.42, P = 0.22). Conclusion FVL may be more common in patients with CVT. However, the association between FVL and CVT varied depending on the geographic origin of the studies.