Objective Systemic anticoagulation remains the standard for acute lower extremity (LE) deep venous thrombosis (DVT), but growing interest in catheter-directed thrombolysis (CDT) and its potential to reduce the incidence of post-thrombotic syndrome (PTS) has led to advent of ultrasound-accelerated CDT (US-CDT). Few studies to date have examined the outcomes of US-CDT against traditional CDT (T-CDT). Methods This is a retrospective, single-center review of all patients treated for acute LE DVT over a five-year period with either US- and T-CDT. Patients were stratified based on demographics, presentation, co-morbidities, risk factors, and peri-procedural data. Results Seventy-six limbs in 67 patients were treated; 51 limbs in 42 patients were treated with US-CDT, and 25 limbs in 25 patients were treated with T-CDT. Adjuncts include: pharmacomechanical thrombolysis ( n = 28 vs. 20, p = 0.04), angioplasty ( n = 22 vs. 18, p = 0.11), stenting ( n = 30 vs. 6, p ≤ 0.001), and IVC filter insertion ( n = 5 vs. 0, p = 0.07). Mean lysis times were 21 ± 1.7 and 24 ± 1.8 h for US- and T-CDT, respectively ( p = 0.26). Thirty (25 ultrasound, 5 traditional) limbs had complete lysis. Thirty-one (22 ultrasound, 9 traditional) limbs had incomplete lysis. Fifteen (4 ultrasound, 11 traditional) limbs had ineffective lysis ( p = 0.002 in favor of ultrasound). Four patients (3 US-CDT, 1 T-CDT) had recurrent ipsilateral thrombosis within 30 days ( p = 0.60). By Kaplan-Meier analysis, there were no significant difference between primary patency, primary-assisted patency, secondary patency, re-thrombosis, and recurrent symptoms at 6, 12, and 24 months. Conclusion US-CDT does not significantly improve mid-term patencies but results in greater acute clot burden reduction in patients with acute LE DVTs compared to T-CDT, which may be beneficial in reducing the long-term incidence of PTS.