PURPOSE:To examine the safety of therapeutic-dose anticoagulation during catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE). MATERIALS AND METHODS:A retrospective review of 156 consecutive cases (age, 56.6 ± 15.4 years; 85 males) of CDT with alteplase for acute PE (symptoms, <14 days) between 2009 and 2019 was performed. All patients received full-dose anticoagulation before, during, and after thrombolysis with low-molecular-weight heparin (LMWH) (n = 45) or unfractionated heparin (n = 111) infusion. Massive PE was diagnosed in 21 of 156 patients at presentation; submassive PE was diagnosed in 135 of 156 patients at presentation. The Simplified Pulmonary Embolism Severity Index was ≥1 in 69 of 156 patients. RESULTS:There were 4 mild (2.6%), 3 moderate (1.9%), and 3 severe (1.9%) hemorrhagic complications (Global Use of Strategies to Open Occluded Arteries), 1 of which (0.6%) was intracranial. No significant differences in hemorrhagic complication rates (P = .3, P = 1.0, and P = .6, respectively) or general complication rates (Society of Interventional Radiology [SIR] minor, P = .2; SIR major, P = .7) were noted between the LMWH and heparin groups. Mean pulmonary arterial pressure for the entire cohort improved from 28.9 ± 7.6 mmHg to 20.4 ± 6.5 mmHg (P < .001), whereas the Miller score improved from 19.3 ± 4.6 to 7.3 ± 3.9 (P < .001). The average infusion duration was 26 ± 11.9 hours over 2.3 ± 0.6 total visits to the angiography lab, during which a mean of 27.85 ± 14.2 mg of tissue plasminogen activator were infused. CONCLUSIONS:Therapeutic anticoagulation during CDT for PE appears to be safe. The current study did not find a significant difference between LMWH and heparin infusion with respect to hemorrhagic and general complication rates.