The optimal duration of oral anticoagulant therapy after a first “unprovoked” venous thromboembolism (VTE) is uncertain. Oral anticoagulation therapy is very efficient in reducing the risk of recurrence but increases the risk of hemorrhage. The balance between the risk of recurrent VTE and bleeding complication is difficult to predict on an individual basis. D-dimer levels during and after anticoagulation cessation have been evaluated in several cohort studies to potentially identify patients at high or low risk of recurrent event. Overall, these studies showed that D-dimer measurement had a high negative predictive value. According to the recent PROLONG trial and a meta-analysis, elevated D-dimer level may help identifying patients with a higher risk for recurrent VTE. Nevertheless, D-dimers should not be used as a stand-alone test to determine whether to stop or continue anticoagulation in patients with a first unprovoked VTE.