OBJECTIVE: To assess the safety, feasibility and efficacy of catheter-directed thrombolysis for thoracic central venous thrombosis in both cancer and non-cancer patients. MATERIALS AND METHODS: A retrospective case series of 68 patients, including 35 with active cancer and 33 without cancer, was analysed. They all received catheter-directed thrombolysis with alteplase or urokinase for symptomatic acute major thoracic vein thrombosis. RESULTS: Substantial clot lysis was obtained in 62 out of 68 patients (91%), the results being 88.6 and 93.8% for cancer and non-cancer patients respectively (P = 0.68). The mean infusion time in patients with and without cancer was 2.11 and 1.84 days respectively (P = 0.3259). Procedure-related complications occurred in two cancer patients (8.6%) and in seven non-cancer patients (21%) (P = 0.18). One cancer patient developed a fatal intracranial bleeding. Additional intervention after successful lysis was performed in cancer (n = 18; 51%) as well as in non-cancer patients (n = 29; 88%). CONCLUSION: Catheter-directed thrombolysis is a feasible and highly effective interventional procedure with an acceptable safety profile in selected patients with and without cancer for the treatment of symptomatic thoracic central venous thrombosis. In most cases, additional endovascular or surgical procedures are required to restore and maintain vessel patency after successful thrombolysis.