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).This was a prospective non-randomised interventional study with US-accelerated CDT for DVT.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.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.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.