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Background: Blood-borne infectious diseases are a major impediment to the provision of safe blood. Pathogen reduction (PR) technologies have been approved for the treatment of plasma and platelet (PLT) concentrates to reduce infectious complications and graft-versus-host disease but product potency is adversely affectedStudy Design and Methods: We reviewed published data describing PR technology for estimates of treated blood component physical and functional loss. These physical and functional losses were summed and projected onto measured effects of plasma and PLT dose in trauma resuscitation. The net benefits estimated as reduced infectious disease deaths were compared to net losses estimated as increased deaths from uncontrolled hemorrhage.Results: Transfusion-transmitted infectious diseases caused five or fewer acute deaths each year from 2009 through 2014 in the United States according to the Food and Drug Administration. In-hospital deaths from uncontrolled hemorrhage after trauma number more than 10,000 yearly and are reduced by 4% to 15% with concentrated blood product resuscitation. The loss of 20% of plasma potency and 30% of PLT potency to PR is likely to be associated with 400 extra trauma deaths each year. Trauma represents a small fraction, perhaps 15%, of all massively transfused individuals.Conclusions: Resuscitation of massive hemorrhage may be limited by blood component potency as shown in our literature review and analysis. The safety-versus-potency trade involved with current blood plasma and PLT PR technology is likely to result in a net loss of life. Hemorrhagic risk from reduced blood product potency for patients with trauma and other indications for massive transfusion is an important consideration in risk-based decision making for implementing PR. [ABSTRACT FROM AUTHOR]