Venous thromboembolism (VTE) affects about 1,200,000 individuals each year in Europe and is associated with a total annual cost ranging from €1.5 to 13.2 billion for the EU-28. About 50% of VTE are unprovoked and 30% will recur after stop of anticoagulant treatment. Guidelines recommend life-long treatment for most of these patients. Thus, most patients receive prolonged anticoagulation whereas their risk of recurrence is low. Available clinical rules have a high sensitivity, but a poor specificity for identifying recurrent VTE and do not allow reducing the proportion of patients receiving prolonged anticoagulant treatment. The scientific network STRATOSPHERE-VTE 2016 will help to personalize treatment duration after a first episode of unprovoked VTE and to reduce the proportion of patients receiving long-term treatment. This will include three steps. • In step 1, we will assess the predictive value of single nucleotide variants, plasma microRNA, proteomic biomarkers, humoral biomarkers and clinical data for the risk of recurrent VTE. A score for predicting recurrent VTE will be derived from available or financially secured data. • In step 2, the score will be externally validated and refined in new prospective cohorts. • In step 3, the effectiveness and medico-economic impact of the score will be evaluated against current practice in a multicenter randomized trial in 1660 patients with unprovoked VTE. By identifying patients at low risk of recurrent VTE, the STRATOSPHERE score will avoid unnecessary life-long anticoagulant treatment with its associated bleeding risk and costs in a substantial proportion of patients with VTE.