OBJECTIVES: Despite recent blood safety advances, a residual risk of pathogen transmission during platelet transfusion remains. Pathogen inactivation using INTERCEPT Platelet System (IPS) has been developed to further reduce these risks. This study assessed the cost effectiveness of IPS for pathogen inactivation of pooled random-donor and single-donor apheresis platelet (RDP-PI and SDP-PI) transfusions. METHODS: A literature-based decision analysis model assessed the cost effectiveness of IPS in US patients receiving SDPs or RDPs. For the baseline analyses, patients were 10-year old female with acute lymphocytic leukemia (ALL), a 50-year old female with non-Hodgkin's lymphoma (NHL), and a 60-year old male undergoing heart surgery (CABG). Pathogen exposure included HIV, HCV, HBV, HTLV-I, bacterial sepsis and new emergent viruses (such as a highly prevalent HIV- or hepatitis-like virus). The model compared projected QALY and costs for patients receiving untreated vs. treated platelets. Univariate sensitivity analyses were performed to test robustness. RESULTS: When minimal benefits were included, incremental cost per QALY of RPD-PI vs. untreated RDPs were $69,000 (ALL), $132,000 (CABG) and $202,000 (NHL). Corresponding figures for SDP-PI were $666,000, $1,420,000, and $2,234,000. When additional benefits such as processing benefits (e.g. shelf-life extension) and new emergent viruses (highly prevalent HIV-like virus) were included, RDP-PI led to increased survival and reductions in costs ($601 for ALL, $86 for CABG, and $1,030 for NHL) whereas the incremental cost per QALY for SDP-PI ranged from $11,000 (ALL), $94,000 (NHL), and $76,000 (CABG). CONCLUSIONS: The cost effectiveness of IPS compares favorably with that of other blood safety interventions (e.g. NAT, ELISA testing) and injury prevention strategies (e.g. school bus seat belt use) that are widely accepted as valuable by society. Thus, platelet inactivation with IPS is a relatively cost-effective strategy to ensure the safety of platelet transfusions and a valuable insurance against the threat of new emerging pathogens.