The aim of this study is to evaluate the plasma total homocysteine level in patients with venous thromboembolism (VTE) and to investigate the effect of different risk factors on plasma levels. Ninety-three-patients with VTE and 37-control participants diagnosed with other than VTE were included in the study. Plasma homocysteine levels and the factors affecting plasma homocysteine levels were evaluated. Plasma homocysteine level was higher among patients with VTE compared to the controls independent from vitamin B12 and folate levels. The prevalence of hyperhomocysteinemia in VTE was 63%. Plasma homocysteine level was higher in patients with PE than deep venous thrombosis (DVT; 23 ± 13.7 vs 16 ± 5.8 μmol/L, P = .018). With regression analysis hyperhomocysteinemia was found to be associated with a 4.8-fold increased risk of VTE. Hyperhomocysteinemia is a common and possibly modifiable risk factor that should be considered when screening patients with VTE. Secondary causes of hyperhomocysteinemia especially vitamin B12 deficiency should be monitored in patients with VTE to prevent recurrences.