Background/Objectives: Ultrasound-assisted catheter-directed thrombolysis (USAT) and mechanical thrombectomy (MT) are increasingly used for intermediate-high-risk pulmonary embolism (PE), but real-world comparisons are scarce. We compare 30-day all-cause, cardiovascular, non-cardiovascular, PE-related, and major bleeding events between intermediate-high-risk patients with acute PE treated with USAT or MT. Methods: We analyzed 286 patients with acute intermediate-high-risk PE enrolled in the multicenter USAT IH-PE registry (March 2019–October 2025). Patients underwent USAT (EKOS™, Boston Scientific, Marlborough, MA, USA) or MT (FlowTriever, Inari Medical, Irvine, CA, USA or Indigo, Penumbra, Inc., Alameda, CA, USA) during index hospitalization. Primary endpoints were 30-day all-cause, cardiovascular, and PE-related mortality. Propensity score matching (1:1) balanced baseline characteristics. Kaplan–Meier analyses with log-rank testing assessed time-to-event outcomes. Results: After matching (69 patients per group), baseline clinical and hemodynamic variables were well balanced. Both USAT and MT significantly improved RV/LV ratio, tricuspid annular plane systolic excursion (TAPSE), and PASP (all p < 0.001). Thirty-day all-cause mortality was similar between USAT and MT (13.0% vs. 11.5%; p = 0.78), with no differences in cardiovascular or PE-related mortality (8.6% vs. 1.4%, p = 0.58 and 5.7% vs. 1.4%, p = 0.17, respectively). Major bleeding was infrequent and observed only in the USAT group (4.3%). Conclusions: In this real-world multicenter cohort, USAT and MT showed comparable short-term mortality, safety, and echocardiographic recovery, supporting individualized catheter-based reperfusion strategies for intermediate-high-risk PE.