Pathogen reduction technology (PRT) enhances blood component safety, but its implementation is hampered by loss of blood quality and cost. A retrospective study was conducted to investigate the efficacy, safety, and cost of 9673 riboflavin and ultraviolet light-treated platelet (PLT) transfusions given to 1211 patients during a 3-year period. The results were compared with the efficacy, safety, and cost of 6424 nontreated PLT transfusions administered to 1500 patients during a 3-year comparison period before PRT implementation. Despite a similar PLT transfusion dose per unit for both periods (pre-PRT period 3.26 vs. PRT period 3.19), the mean number of PLT concentrates per patient (4.2 vs. 7.8; p = 0.006) and the total dose of PLTs received by patients were higher in the PRT period (13.6 vs. 24.8; p = 0.0002). Hematology and medical and surgical patient categories had the highest PLT use per patient. However, febrile (2.5% vs. 1.2%; p = 0.02) and allergic (0.16% vs. 0.08%; p = 0.01) reactions were lower during the PRT period. The blood center saved €284,805.58 due to a reduction of outdated PLTs from 16.8% to 0.72% after PRT implementation. Although PRT can improve PLT safety, it can increase the amount of PLTs required for transfusion in some patient categories. The cost of PRT can be partially offset by the savings associated with a lower rate of PLT outdates. This cost reduction can be a key factor in settings where inventory management is challenged by a high percentage of wasted PLTs due to outdating.