Ultrasound-accelerated thrombolysis (USAT) is an advanced interventional therapy for patients with intermediate–high-risk pulmonary embolism (PE) who deteriorated on anticoagulation or for high-risk patients for whom systemic thrombolysis is contraindicated. The aim of this study is to investigate the safety and efficacy of this therapy with a focus on the improvement of vital signs and laboratory parameters. Seventy-nine patients with intermediate–high-risk PE were treated with USAT from August 2020 to November 2022. The therapy significantly decreased the mean RV/LV ratio from 1.2 ± 0.22 to 0.9 ± 0.2 (p< 0.001) as well as the mean PAPs from 48.6 ± 11 to 30.1 ± 9.0 mmHg (p< 0.001). The respiratory and heart rate decreased significantly (p< 0.001). Serum creatinine decreased significantly from 1.0 ± 0.35 to 0.9 ± 0.3 (p< 0.001). There were 12 access-associated complications, which could be treated conservatively. One patient had haemothorax after the therapy and had to be operated on. USAT is an effective therapy for patients with intermediate–high-risk PE, with favourable hemodynamic, clinical, and laboratory outcomes.