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The use of resuscitative endovascular balloon occlusion as a maneuver for occlusion of the aorta is well described. This technique has life-saving potential in other cases of traumatic hemorrhage. Retrohepatic inferior vena cava (IVC) injuries have a high rate of mortality, in part, due to the difficulty in achieving total vascular isolation. The purpose of this study was to investigate the ability of resuscitative balloon occlusion of the IVC to control suprahepatic IVC hemorrhage in a swine model of trauma.Thirteen swine were randomly assigned to control (seven animals) versus intervention (six animals). In both groups, an injury was created to the IVC. Hepatic inflow control was obtained via clamping of the hepatoduodenal ligament and infrahepatic IVC. In the intervention group, suprahepatic IVC control was obtained via a resuscitative balloon occlusion of the IVC placed through the femoral vein. In the control group, no suprahepatic IVC control was established. Vital signs, arterial blood gases, and lactate were monitored until death. Primary end points were blood loss and time to death. Lactate, pH, and vital signs were secondary end points. Groups were compared using the χ2 and the Student t test with significance at p < 0.05.Intervention group's time to death was significantly prolonged: 59.3 ± 1.6 versus 33.4 ± 12.0 minutes (p = 0.001); and total blood loss was significantly reduced: 333 ± 122 vs 1,701 ± 358 mL (p = 0.001). In the intervention group, five of the six swine (83.3%) were alive at 1 hour compared to zero of seven (0%) in the control group (p = 0.002). There was a trend toward worsening acidosis, hypothermia, elevated lactate, and hemodynamic instability in the control group.Resuscitative balloon occlusion of the IVC demonstrates superior hemorrhage control and prolonged time to death in a swine model of liver hemorrhage. This technique may be considered as an adjunct to total hepatic vascular isolation in severe liver hemorrhage and could provide additional time needed for definitive repair.Therapeutic study, level II.