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Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has been used clinically to limit torso bleeding and restore central perfusion. The objective of this study was to determine the sequelae of prolonged REBOA in a nonhuman primate animal model.Prolonged duration of REBOA is associated with adverse clinical outcomes. Threshold occlusion values tied to relative risk have yet to be determined.Juvenile baboons were subjected to 40% to 55% total blood volume hemorrhage to achieve profound hypotension and shock. Zone I REBOA was performed for 60 minutes to assess acute injury and survival at 4 hours (group 1; n = 7). Post-REBOA 10-day survival and complications were then compared between 60 minutes (group 2; n = 8) and 30 minutes (group 3; n = 6) REBOA animals.Overall survival was 20/21 (95%). IL-6 and IL-8 were elevated at 1 and 4 hours in group 1 (P = 0.005; P = 0.001). Comparing 60-minute REBOA with 30-minute REBOA, there was (1) hypertension compared with normotension (P = 0.005), (2) increased base deficit (P = 0.003), (3) elevated Troponin I (P = 0.04), and histological evidence of kidney injury (P = 0.004). In addition, group 2 demonstrated paralysis with histopathologic changes of spinal cord ischemia (SCI) in 4/8 (50%), with no SCI in group 3 (P = 0.033).REBOA limits mortality in the primate model of severe hemorrhagic shock. However, unopposed balloon inflation in the distal thoracic aorta for 60 minutes results in high rates of spinal cord ischemia, an effect mitigated by limiting balloon inflation to 30 minutes.