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High-grade solid organ injury is a major cause of mortality in trauma. Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) can be effective but is limited by ischemia-reperfusion injury. Intermittent balloon inflation/deflation has been proposed as an alternative, but the safety and efficacy prior to operative hemorrhage control is unknown.Twenty male swine underwent standardized high-grade liver injury, then randomization to controls (N = 5), 60-min continuous REBOA (cR, n = 5), and either a time-based (10-minute inflation/3-minute deflation, iRT = 5) or pressure-based (mean arterial pressure<40 during deflation, iRP = 5) intermittent schedule. Experiments were concluded after 120 minutes or death.Improved overall survival was seen in the iRT group when compared to cR (p < 0.01). Bleeding rate in iRT (5.9 mL/min) was significantly lower versus cR and iRP (p = 0.02). Both iR groups had higher final hematocrit (26% vs. 21%) compared to cR (p = 0.03). Although overall survival was lower in the iRP group, animals surviving to 120 minutes with iRP had decreased end organ injury (Alanine aminotransferase [ALT] 33 vs. 40 in the iRT group, p = 0.03) and lower lactate levels (13 vs. 17) compared with the iRT group (p = 0.03). No differences were seen between groups in terms of coagulopathy based on rotational thromboelastometry.Intermittent REBOA is a potential viable adjunct to improve survival in lethal solid organ injury while minimizing the ischemia-reperfusion seen with full REBOA. The time-based intermittent schedule had the best survival and prolonged duration of tolerable zone 1 placement. Although the pressure-based schedule was less reliable in terms of survival, when effective, it was associated with decreased acidosis and end-organ injury.