Background: Few data are available on the outcomes of patients with venous thromboembolism (VTE) on long-term reduced dose of direct oral anticoagulants (DOACs). We evaluated the effectiveness and safety of reduced dose of DOACs for the extended treatment of VTE. Methods: In this monocenter, ambispective cohort study, 140 patients receiving a reduced dose of DOACs for VTE were included. The primary outcomes were recurrent VTE, major bleeding and clinically relevant non-major bleeding. The secondary outcomes were arterial events and minor bleedings. The incidence of the primary outcomes was calculated. The rate for secondary outcomes was descriptively reported. Results: The mean age of the overall cohort was 72 years. Half of the patients were female, 51.4% had a persistent risk factor, 40.0% an unprovoked VTE, and 8.6% a minor transient risk factor. Most patients had lower extremity deep vein thrombosis with or without pulmonary embolism (55.0%) and received apixaban (73.6%) or rivaroxaban (14.3%) for a mean duration of 2.7 years. Regarding the primary outcomes, there was one recurrent VTE (0.7%), four major bleedings (2.9%) and two clinically relevant non-major bleedings (1.4%). Regarding the secondary outcomes, there were four acute ischemic strokes (2.9%) and two minor bleedings (1.4%). Conclusions: Reduced dose of DOACs was associated with a low rate of recurrent VTE and an acceptably low rate of bleeding complications. The rate of arterial events during follow-up suggests the need for an assessment of cardiovascular risk factors in this study population.