OBJECTIVE: The residual risk of transmitting current and emerging infectious blood-borne pathogens via blood transfusion persists despite recent blood safety advances. The INTERCEPT Blood System (IBS) for platelets has been developed to further reduce these pathogen transmission risks during platelet transfusions. The objective of this study was to assess the cost-effectiveness of using single-donor (aphaeresis) platelets (SDP) processed with IBS in Japan. METHODS: A literature-based decision analysis model was used to assess the cost-effectiveness of the IBS in four patient populations that account for most of the platelet usage in Japan: 1) a 10-year old male with acute lymphocytic leukaemia (ALL); 2) a 50-year old male with non-Hodgkin's lymphoma (NHL); 3) a 60-year old male undergoing heart bypass surgery (CABG); and 4) a 70-year old female undergoing a hip arthroplasty. Pathogen exposure included HIV, HCV, HBV, HTLV-I, bacterial sepsis, emerging and migrating pathogens. The model compared projected quality-adjusted life-year saved (QALY) and costs for patients receiving untreated vs. treated platelets. RESULTS: The incremental cost per QALY gained by using SDP+IBS vs. SDP ranged from ¥96,248,673 – ¥793,899,885. Inclusion of a hepatitis C-like emerging pathogen benefit significantly improved the cost effectiveness to ¥20,534,864 – ¥434,648,944. The model was most sensitive to mortality from bacterial contamination and the risk rate of emerging and/or migrating pathogens. The model was relatively insensitive to transmission risks from currently known viruses. CONCLUSION: The cost-effectiveness of IBS for platelets is comparable and mostly better to that of other blood and general safety interventions (e.g., mini-pool NAT testing, chemical regulations, traffic safety measures) that are accepted as valuable in Japan. Thus, pathogen inactivation with IBS may be considered as a desirable strategy to further improve the safety of platelet transfusions and a valuable insurance against the threat of new emerging and migrating pathogens.