BACKGROUND: Bacterial contamination is a life-threatening risk of blood transfusion, especially with platelet (PLT) transfusions. Bacterial culturing (BCU) of PLTs as well as pathogen reduction (PRT) reduce the likelihood of such contamination. The cost-effectiveness (CE) of these interventions was analyzed after the introduction of the diversion pouch during blood collection. STUDY DESIGN AND METHODS: The balance between costs and benefits of preventing adverse events due to PLT transfusion was assessed with a mathematical decision model and Monte Carlo simulations. Model parameters were obtained from the literature and from Dutch Sanquin blood banks. The balance between costs and benefits is assessed in terms of costs per quality-adjusted life-year (QALY). RESULTS: The costs per 100,000 PLT concentrates in the Netherlands are estimated at $3,277,032 (€2,520,794) for BCU and at $18,582,844 (€14,294,495) for PRT. In comparison to the situation without BCU and PRT, costs per QALY are estimated at $90,697 (€69,767) for BCU (95% confidence interval [CI], $18,149-$2,088,854) and at $496,674 (€382,057) for PRT (95% CI, $143,950-$8,171,133). The ratio of differences in costs and QALYs between BCU and PRT (the relative CE) is estimated at $3,596,256 (€2,766,351; 95% CI, $1,100,630-$24,756,615). Large uncertainty in sepsis complication rates and PLT recipient survival exist, causing large uncertainties in the absolute CE for both interventions. CONCLUSIONS: As a result of the unknown probability of sepsis complications and PLT recipient survival, the CE ratios of BCU and PRT in the Dutch setting are highly uncertain. Despite these large uncertainties, it can be concluded that BCU is without doubt more cost-effective than PRT.