The natural history of initially positive D-dimers for venous thromboembolism is not known. If it returns to negative in the majority of patients, it would be potentially helpful to diagnose a recurrence. In this study, we prospectively measured D-dimer levels in outpatients with a diagnosis of venous thromboembolism. There were a total of 152 patients with an average age of 57. D-dimer results were performed at baseline and repeated at one week, one month and three months. At baseline 120 of 152 (79%) had a positive D-dimer result. Of those with an initially positive result, 80% were still positive at one week and 39% were still positive at one month. Finally at three months, 13% remained positive. Seven patients had recurrent events and all had persistently elevated D-dimers at one month. This study suggests that a persistently positive D-dimer result after one month of treatment may indicate a higher risk of recurrent venous thromboembolism. D-dimer testing for the diagnosis of recurrence of venous thromboembolism deserves further study.