Deep vein thrombosis (DVT) of the lower limbs is a frequent and serious condition associated with severe complications, including post-thrombotic syndrome (PTS) and severe chronic venous insufficiency, which significantly impact the quality of life and induce high medical expenses. Current DVT management fails to prevent PTS. Therapeutic anticoagulation for DVT has little impact on PTS, potentially because of a lack of effective spontaneous venous recanalization. Ultrasound thrombotripsy has been proposed as a new non-invasive therapy, using short intense ultrasound pulses focused precisely in the thrombotic region to destroy the thrombus. The therapy is non-invasive, and guided in real-time using ultrasound imaging. So far, it has never been used on human because clinical translation requires important technological advances. The goal of this project is to develop a clinical prototype for the non-invasive ultrasound treatment of DVT and to carry out the first clinical proof of concept on patients. The clinical prototype will be based on a multi-element therapeutic ultrasound to move electronically the focus and address the range of focusing depth required in human patients. Real-time imaging guidance will be provided by an ultrasound imaging linear array embedded in the system. The entire system will be moved and assisted by a robotic arm. Imaging, therapy and robotic systems will be integrated on the same system and controlled by dedicated user interface software at each step of the treatment. The entire system will be developed and integrated in compliance with the international standards of medical devices. The clinical prototype will be validated by in vitro and in vivo preclinical experiments. Finally, the first-in-human study will include 10 patients with disabling PTS.