Background and objectives: To assess the predictive value of D-dimer (D-d) and Factor VIII (FVIII) in combination for recurrent venous thromboembolism (VTE) after vitamin K antagonist (VKA) therapy suspension. Design and methods: Consecutive outpatients with a first episode of idiopathic proximal deep vein thrombosis of the lower Limbs were enrolled on the day of VKA suspension. After 30+/-10 days, D-d (cut-off value: 500 ng/mL), chromogenic FVIII activity and inherited thrombophilia were determined. Follow-up was 2 years. Results: Overall recurrence rate was 16.4% (55/336; 95% Cl:13-21%). The multivariate hazard ratio (HR) for recurrence was 2.45 (95%Cl: 1.24-4.99) for abnormal D-d and 2.76 (95% Cl:1.57-4.85) for FVIII above the 75th percentile(2.42 U/mL) after adjustment for age, sex, thrombophilia, VKA duration and residual venous obstruction. When compared with normal D-d and FVIII, the multivariate HR was 4.5 (95% Cl: 1.7-12.2) for normal D-d with FVIII above 2.42 U/mL and 2.7 (95% Cl: 1.2-6.6) and 7.1 (95% Cl:2.8-17.6) for abnormal D-d with FVIII, respectively, below and above 2.42 U/mL. Interpretation and conclusions: D-d and FVIII at 30+/- 10 days after VKA withdrawal are independent risk factors for recurrent VTE. (C) 2008 Elsevier Ltd. All rights reserved.