Hyperhomocysteinemia (HHC) is an independent risk factor for cardiovascular disease, and even mildly to moderately elevated homocysteine levels have been associated with a heightened risk for a first and recurrent venous thromboembolism (VTE). Within the frame of a large prospective cohort study (Austrian Study on Recurrent Venous Thromboembolism), we assessed the impact of HHC on the risk of recurrence among 602 patients with a first unprovoked VTE. HHC was an independent risk factor of recurrence conferring a relative risk of 1.5 (95th% CI 1.0-2.4). HHC is caused either by genetic defects and/or by a deficiency of the vitamins (B12, B6 and folic acid) involved in the homocysteine metabolism. Low vitamin B6 levels are associated with an increased risk of a first venous thrombosis. We currently investigate whether or not low plasma levels of PLP are associated with a heightened risk for recurrent VTE.