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BACKGROUND: There is debate whether astronauts traveling to space should undergo a prophylactic splenectomy prior to long duration spaceflight. Risks to the spleen during flight include radiation and trauma. However, splenectomy also carries significant risks.METHODS: Systematic review of data published over the past 5 decades regarding risks associated with splenectomies and risks associated with irradiation to the spleen from long duration spaceflight were analyzed. A total of 41 articles were reviewed.RESULTS: Acute risks of splenectomy include intraoperative mortality rate (from hemorrhage) of 3-5%, mortality rate from postoperative complications of 6%, thromboembolic event rate of 10%, and portal vein thrombosis rate of 5-37%. Delayed risks of splenectomy include overwhelming postsplenectomy infection (OPSI) at 0.5% at 5 yr post splenectomy, mortality rate as high as 60% for pneumococcal infections, and development of malignancy with relative risk of 1.53. The risk of hematologic malignancy increases significantly when individuals reach 40 Gy of exposure, much higher than the 0.6 Gy of radiation experienced from a 12-mo round trip to Mars. Lower doses of radiation increase the risk of hyposplenism more so than hematologic malignancy.CONCLUSION:For protection against hematologic malignancy, the benefits of prophylactic splenectomy do not outweigh the risks. However, there is a possible risk of hyposplenism from long duration spaceflight. It would be beneficial to prophylactically provide vaccines against encapsulated organisms for long duration spaceflight to mitigate the risk of hyposplenism.Siu M, Levin D, Christiansen R, Kelly E, Alouidor R, Kamine TH. Prophylactic splenectomy and hyposplenism in spaceflight. Aerosp Med Hum Perform. 2022; 93(12):877-881.