BACKGROUND:Comparative data on ultrasound-assisted catheter-directed thromboly-sis (USAT) and systemic low-dose tissue-type plasminogen activator (tPA) for intermediate-high-risk (IHR) pulmonary embolism (PE) remain limited. The efficacy and safety outcomes of USAT vs. intravenous (IV) low-dose tPA were evaluated in this population. METHODS:This study enrolled 329 IHR PE patients treated with USAT (n = 205) or IV low-dose tPA (n = 124). Post-treatment changes in clot burden (Qanadli score), right ventricular (RV) strain, and long-term mortality (median follow-up 95.8 months) were assessed. Propensity score analysis with inverse probability weighting (IPW) was employed to adjust for confounders. RESULTS:Ultrasound-assisted catheter-directed thrombolysis was predominantly bilateral (82.9%), with a mean tPA dose of 38.5 ± 13.6 mg. In the IV tPA cohort, 58.9% required a second infusion to achieve stabilization. While IV tPA was associated with more pronounced early reductions in heart rate and RV/LV (left ventricle) ratio, USAT provided significantly greater thrombus resolution (all P < .005). After IPW adjustment, USAT demonstrated clear superiority over IV tPA in reducing residual clot burden (P < .001). However, improvements in oxygen saturation, tricuspid annular plane systolic excursion , and pulmonary artery systolic pressure (PASP) were comparable. No significant differences were observed in in-hospital mortality, PE recurrence, or long-term survival between cohorts. Higher PE severity indexes scores independently predicted in-hospital adverse events, whereas older age, male sex, and higher discharge PASP were predictors of shortened long-term survival. CONCLUSIONS:In IHR PE, IV low-dose tPA relates to more pronounced early hemodynamic and RV diameter improvements, whereas USAT achieves superior thrombus resolution. Despite these divergent surrogate responses, both strategies yield comparable early and long-term clinical outcomes, supporting their roles as viable reperfusion options.