Residual risk of transmitting recognized and emerging blood-borne pathogens via blood transfusion in Japan persists despite advances in blood safety screening. The INTERCEPT Blood System (IBS) for platelets was developed to inactivate a broad spectrum of pathogens to reduce the risk of transfusion-transmitted infections. In this study we assessed the economic impact of the IBS on platelet transfusion costs. An economic analysis model was used to assess both net cost and cost-effectiveness of the IBS for the patient populations accounting for most of the platelet use in Japan. Pathogen exposure included viruses currently recognized to cause transfusion-transmitted infections and emerging pathogens of potential significance for transfusion-transmitted infections. Economic assessment of the full potential of the IBS revealed that only a small increase in net cost can be expected with implementation. The cost-effectiveness of the IBS for platelets is comparable with and potentially better than that of other blood safety interventions (eg, nucleic acid testing) and, in general, other recently implemented safety interventions (eg, chemical regulations and traffic safety measures) accepted as valuable in Japan. Thus a preventive approach using pathogen inactivation with the IBS may be considered a desirable strategy for improving the current safety of platelet transfusions in Japan.