BACKGROUND:The optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to accurately assess the effect of anticoagulant therapy in reducing recurrent VTE against the risk of inducing major bleeding. METHODS:Randomized controlled trials were identified by searching PubMed, Web of Science, Embase, and the Cochrane library, reporting rates of recurrent VTE and major bleeding in patients taking Vitamin K Antagonists (VKA) with VTE and comparing different durations. RESULTS:Eleven RCTs with 3109 participants utilizing varied durations were included in the meta-analysis. Longer VKA therapy was associated with significantly lower rates of VTE recurrence compared with shorter duration of VKA therapy (OR 0.75, 95%CI 0.57-0.99), with significant difference noted in major bleeding risk (OR 2.31, 95%CI 1.17-4.56). During anticoagulation duration, patients treated by 6-month VKA had higher risk of major bleeding compared with 3-month VKA regimen (OR 33.45, 95%CI 2.00-559.67). CONCLUSIONS:Regimen longer than 6 months did not show statistical elevation of major bleeding risk. VKA treatment strongly reduces the risk of recurrent VTE during anticoagulation therapy. The absolute risk of recurrent VTE declines over time while the risk for major bleeding after 6 months' treatment did not demonstrate a continuous significant increase with extended duration of VKA therapy.