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Intermediate-risk pulmonary embolism (PE), also known as submassive PE, occurs in a substantial group of patients and carries a significant mortality risk. With adequate risk stratification, catheter-directed techniques could be used as a therapeutic approach in the intermediate-risk PE. Ultrasound-assisted catheter-directed thrombolysis (UCDT) represents a novel endovascular technique with good clinical and safety outcomes. Ultrasound-assisted catheter-directed thrombolysis can achieve reduction in the thrombus burden and improvement of pulmonary hemodynamics and right ventricular (RV) dysfunction and/or dilatation, without major procedure-related complications, major bleeding, or hemorrhagic strokes. This narrative review will focus on the major studies involving the efficacy and safety of UCDT in the intermediate-risk PE population. Prospective, randomized clinical trials with long-term follow-up and a large sample size are needed for further evaluation of mortality benefit and to further define which subgroup of patients may benefit from this novel endovascular technique.