Blood clot formation in vein, known as venous thromboembolism is a major disease worldwide. Ultrasound and laser-based treatment techniques have been developed to remove blood clots and recanalize occluded vessels. The applications of both technologies are hindered by their individual limitations. We tested a novel hybrid technology based on the spatio-temporally synchronized pulsed laser and ultrasound, namely, ultrasound-assisted endovascular laser thrombolysis (USELT) in an in-vitro- blood clot model and invivo rabbit model. The in vitro- study demonstrated enhanced thrombolysis with USELT as compared with ultrasound-only and laser-only. In in vivo study, out of seven treated rabbits in USELT group, the vein was fully or partially recanalized in five rabbits and poorly recanalized in two rabbits, whereas the vein treated with ultrasound-only and laser-only did not result in recanalization in any case. The in vitro- and in vivo study successfully demonstrated the feasibility of USELT for thrombolysis, and USELT has the potential to combine the advantages of both ultrasound and laser thrombolysis techniques and overcome their limitations.