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Background: Intrapleural lytic therapy has been established as an important modality of treatment for many pleural disorders, including hemothorax and empyema. Retained traumatic hemothorax is a common and understudied subset of pleural disease. The current standard of care for retained traumatic hemothorax is operative management. The use of lytic therapy for avoidance of operative intervention in the trauma population has not been well established., Methods: Randomized controlled trials (RCTs) and non-RCTs reporting operative intervention following the use of intrapleural lytic treatment for retained traumatic hemothorax were identified in the literature. The primary outcome was avoidance of surgery following treatment with any lytic agent. Meta-analysis was performed to pool the results of those studies. Subgroup analysis by type of lytic therapy and analysis of length of stay were also performed., Results: One RCT and nine non-RCTs including 162 patients were pooled in the analysis. Avoidance of surgery following treatment with any lytic agent was found to be 87% (95% CI, 81%-92%). Tissue plasminogen activator resulted in 83% operative avoidance (95% CI, 71%-94%), and other, non-tissue plasminogen activator lytic agents resulted in 87% operative avoidance (95% CI, 82%-93%). The average length of stay for patients undergoing lytic therapy was 14.88 days (95% CI, 12.88-16.88)., Conclusions: Lytic therapy could reduce the need for operative intervention in trauma patients with retained traumatic hemothorax. RCTs are indicated to definitively evaluate the benefit of this approach., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)