Background Experience with early postoperative catheter-directed ultrasound-assisted thrombolysis (USAT) in high-risk pulmonary embolism (PE) is limited. A first case of USAT directly after pulmonary surgery is presented. Case Description A 60-year-old female patient with two malignancies (triple negative breast cancer and pulmonary squamous cell carcinoma) underwent video-assisted lobectomy. The second postoperative day, she developed PE with hemodynamic deterioration. Note that 24 mg of alteplase was applied by USAT. After 3 days she was successfully weaned from ventilation and vasopressors. Conclusion USAT for acute PE is possible after major pulmonary resections and seems promising if reperfusion is needed.