Homocysteine is an amino acid derived from methionine, metabolized via vitamin B6 (pyridoxine)- and vitamin B12 (cobalamin)-dependent pathways. Supplementation of B vitamins has been shown to effectively reduce plasma homocysteine levels. Previous research has also demonstrated an association between lower plasma homocysteine levels and decreased risk of myocardial infarction, stroke and venous thromboembolism. However, it remains inconclusive if supplementation of B vitamins is associated with risk reduction in thromboembolic events and confers clinical benefits. This article aims to review clinical trials in the last ten years to determine the effects of B vitamin supplementation in plasma homocysteine lowering, and evaluate its impact on reducing the risk of arterial and venous thromboembolism.