It is unclear if ultrasound-assisted catheter-directed thrombolysis (UACDT) confers benefit over anticoagulation (AC) alone in the management of intermediate-risk (“submassive”) pulmonary embolism (PE), defined by evidence of right ventricular (RV) dysfunction in hemodynamically stable patients. This study sought to evaluate any lasting advantage of UACDT on mortality and resolution of RV dysfunction in intermediate-risk PE at a large academic medical center. Adults aged ≤ 86 years admitted with intermediate-risk PE from 2011 to 2016 were retrospectively identified. Patients were excluded if there was a history of cancer, pre-existing pulmonary hypertension, pregnancy or postpartum status, contraindication to AC, or treatment with systemic thrombolysis. Baseline Pulmonary Embolism Severity Index (PESI) scores were computed. Outcomes including length of stay (LOS), bleeding complications, resolution of RV dysfunction, and mortality were compared between patients who received UACDT and those managed with AC alone. A total of 104 patients met inclusion criteria, 65 of whom underwent UACDT. The cohorts had similar PESI scores (P = 0.45) and no clearly imbalanced confounding variables. There was no significant difference in LOS (P = 0.11). UACDT was associated with more bleeding complications (exact P = 0.04). Follow-up transthoracic echocardiograms performed in 54 UACDT and 24 AC patients demonstrated similar rates of resolution of RV dysfunction (61% in UACDT patients versus 75% in AC patients, P = 0.25). Overall one-year mortality was approximately 5% in both groups (exact P > 0.99). In this limited retrospective analysis of intermediate-risk PE patients, UACDT treatment was not associated with mortality benefit or increased resolution of RV dysfunction.