Spontaneous axillary-subclavian vein thrombosis in young patients produces long-term disability. Patients with secondary axillary-subclavian vein thrombosis usually require prolonged venous catheterization for chemotherapy or pacemaking. This study aimed to compare the early and late results of lytic versus anticoagulant therapy in the treatment of axillary-subclavian vein thrombosis, both spontaneous and secondary to central venous cannulation. Nine patients underwent conventional treatment (heparin and warfarin) (group 1), and 10 had initial lytic therapy followed by heparin and warfarin (group 2). Three patients had cervical or first rib resection. Thirteen patients had spontaneous thrombosis and six were secondary to central venous catheterization. The mean follow-up was 36 months. Two of nine patients (22%) in group 1 and eight of 10 patients (80%) in group 2 had total venous recanalization and symptom resolution (P = 0.018). In the spontaneous axillary-subclavian vein thrombosis subset, one of six patients (17%) in group 1 and five of seven patients (71%) in group 2 had total venous recanalization and symptom resolution (P = 0.078). The average difference in cost per patient between groups 1 and 2 was $19,039. In conclusion, lytic therapy appears superior to anticoagulation in the treatment of axillary-subclavian vein thrombosis. However, such treatment is more expensive and its benefits should be carefully weighed against the cost in each case.