Clinical trials evaluating antithrombotic therapy for the treatment of deep vein thrombosis require that the diagnosis is confirmed by objective testing prior to patient entry into the study. Two basic approaches may then be taken for defining endpoints to assess the efficacy of antithrombotic treatment. In the first approach, the diagnostic test is repeated at a predetermined time following the initiation of the interventional therapy. In the second approach, no further diagnostic testing is routinely performed for a minimum of 3 months following patient enrolment after the diagnosis of venous thromboembolism for evidence of symptomatic recurrent deep vein thrombosis or pulmonary embolism. This approach is used in later-phase clinical trials to examine whether a novel therapeutic agent is as safe and effective as the drugs currently used for management of venous thromboembolism. Symptomatic recurrent deep vein thrombosis and pulmonary embolism confirmed by objective testing are clinically important causes of patient morbidity, place patients at increased risk of fatal pulmonary embolism, cause increased rates of chronic thromboembolic complications and have resource consequences. Studies utilizing symptomatic recurrent deep vein thrombosis or pulmonary embolism as endpoints have been responsible for most of the treatment advances in the management of patients with venous thromboembolism that have been observed in the past 40 years. Although confirmation of recurrent venous thromboembolism is not possible in all patients, clinical trials using rigorous methodology can minimize the potential bias caused by the limitations of diagnostic test results. There is a need to develop better objective tests in the future, to distinguish previous from recurrent venous thromboembolism.