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Abstract: Objective: One in four patients with primary iliofemoral deep vein thrombosis (DVT) develops post-thrombotic syndrome (PTS) within 1 year despite optimal standard anticoagulant therapy. Removal of thrombus by thrombolytic drugs may prevent PTS. The aim of this study was to assess the short-term safety and efficacy of ultrasound-accelerated catheter-directed thrombolysis (US-accelerated CDT). Design: This was a prospective non-randomised interventional study with US-accelerated CDT for DVT. Patients and methods: Twelve patients with DVT (seven caval–iliofemoropopliteal, three iliofemoropopliteal, one femoropopliteal and one superior caval vein thrombosis) receiving standard anticoagulant and compression therapy, were treated with additional US-accelerated CDT (13 procedures) using the EKOS Endowave® system (EKOS Corporation, Bothell, WA, USA) between October 2008 and January 2010. Results: Thrombolysis was successful in 85% (11/13), with complete clot lysis (>90% restored patency) and in one case with partial clot lysis (50–90% restored patency). No pulmonary embolism and one bleeding at the catheter-insertion site were observed. In three patients, underlying lesions were successfully treated with balloon angioplasty and stent insertion. Four patients developed early recurrent thrombosis due to untreated residual venous obstruction. Conclusion: US-accelerated CDT is a safe and promising treatment in patients with DVT. Residual venous obstruction should be treated by angioplasty and stent insertion to avoid early re-thrombosis. [Copyright &y& Elsevier]