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Background: The optimal therapy for submassive pulmonary embolism remains in question. The following meta-analysis compiles the current evidence comparing Catheter-Directed Thrombolysis (CDT) versus Systemic Anticoagulation (SA). Methods: An electronic search through PubMed and Google scholar revealed studies comparing CDT versus SA in terms of mortality and major bleeding events. Thirty-day, 90-day, and one-year mortality results were analyzed. Results: Six studies were included in the meta-analysis. Thirty-day and one-year mortality were less with CDT compared to SA (OR 0.27 [CI 0.11-0.67]; and OR 0.50 [CI 0.28-0.89]). Ninety-day mortality was similar between the two methods (OR 0.57 [CI 0.17-1.92]). Compilation of all studies reporting at least greater than 30-day mortality revealed less mortality with CDT (OR 0.51 [0.30-0.86]). Major bleeding was similar between the two treatments (OR 1.63 [CI 0.63-4.20]). Conclusion: CDT has less 30-day and 1-year mortality with equivalent rates of major bleeding compared to SA for treatment of submassive pulmonary embolism.