Background: Traumatic hemorrhage is a leading preventable cause of mortality following mass casualty events (MCEs). Improving outcomes requires adequate in-hospital provision of high volume red blood cell (RBC) transfusions. This study investigated strategies for optimizing RBC provision to casualties in MCEs using simulation modeling. Methods: A computerized simulation model of a UK major trauma centre (TC) transfusion system was developed. The model used input data from past MCEs, civilian and military trauma registries. We simulated the effect of varying on-shelf RBC stock hold and the timing of externally restocking RBC supplies on TC treatment capacity across increasing loads of priority one (P1) and two (P2) casualties from an event. Results: 35,000 simulations were performed. A casualty load of 20 P1&2s under standard TC RBC stock conditions left 35% (95% CI 32-38) of P1s and 7% (4-10) of P2s inadequately treated for hemorrhage. Additionally, exhaustion of type O emergency RBC stocks (a surrogate for reaching surge capacity) occurred in a median of 10 hours (IQR 5->12). Doubling casualty load increased this to 60% (57-63) and 30% (26-34) respectively with capacity reached in 2hours (1-3). The model identified a minimum requirement of 12U of on-shelf RBCs per P1/2 casualty received to prevent surge capacity being reached. Restocking supplies in an MCE versus greater permanent on-shelf RBC stock holds was considered at increasing hourly intervals. T-test analysis showed no difference between stock hold versus supply restocking in terms of overall outcomes for MCEs up to 80 P1&2s in size (p<0.05), provided the restock occurred within 6 hours. Conclusion: Even limited sized MCEs threaten to overwhelm TC transfusion systems. An earlyautomated push approach to restocking RBCs initiated by central suppliers can produce equivocal outcomes compared with holding excess stock permanently at TCs.