A homocysteine-independent role for B-group vitamins on venous thrombosis (VT) development has been reported. However, related research findings remain inconsistent. PUBMED, EMBASE, and COCHRANE databases were searched to collect information on all eligible studies to make a meta-analysis about the relationship between B-group vitamins and VT. Literature search results did not suggest a correlation between thiamin, pantothenic acid, niacin, or riboflavin with VT. Based on their correlations in the literature, folic acid, vitamin B12, B6 were considered in the meta-analysis and systematic review. Significant standardized mean differences were obtained for plasma folic acid (-0.55; 95 % CI, -0.75 to -0.36) and vitamin B12 (-0.34; 95 % CI, -0.55 to -0.13). Reduced levels of folic acid and vitamin B12 may be independent risk factors of VT. Moreover, a qualitative systematic review indicated that low level of vitamin B6 was an independent risk factor of VT. Randomized clinical studies of B-group vitamins supplementation showed varying results on VT prevention. Multivitamin supplementation for VT prevention, regardless of homocysteine level, would be of interest. Further prospective clinical studies are needed to provide additional evidence on the clinical benefits of B-group vitamin supplementation for VT.