OBJECTIVE: The residual risk of transmitting 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 random-donor platelets (RDP) and single-donor platelets (SDP) processed with IBS in Spain. 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 Spain: 1) a 10-year-old male with acute lymphocytic leukemia (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 and emerging 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 RDP+IBS vs. RDP ranged from €386,525- €1,178,187. Corresponding figures for SDP+IBS vs. SDP ranged from €1,082,170- €2,805,297. Inclusion of an emerging pathogen benefit significantly improved the cost effectiveness to €65,423- €307,311 for RDP and €300,793- €1,223,349 for SDP. The model was most sensitive to mortality from bacterial contamination and the number of additional platelet transfusions required due to IBS treatment. The model was relatively insensitive to transmission risks from currently known viruses. CONCLUSION: The cost effectiveness of IBS for platelets is comparable to that of other blood safety interventions (e.g., NAT, plasma inactivation) that are accepted as valuable in Spain. Thus, pathogen inactivation with IBS may be considered as a desirable strategy to ensure the safety of platelet transfusions and a valuable insurance against the threat of new emerging pathogens.