Despite recent advances in blood screening techniques, transfusions are not risk-free. Therefore, screening for viral and bacterial infections as well as other, newly-emerging agents continues to attract attention in the medical and health policy communities. At the same time, governments and other decision-making bodies increasingly use cost-effectiveness analyses to justify (or reject) allocation of limited financial resources to new technologies. OBJECTIVES: To assess the cost-effectiveness of commonly employed blood safety interventions, and compare those cost effectiveness levels with other accepted injury prevention measures. METHODS: Using MEDLINE, we conducted a literature review on the cost-effectiveness of various transfusion-relevant blood safety interventions. We identified 16 studies (published between 1993 and 2000) of blood safety interventions that evaluated their economic benefit as either a cost per QALY or cost per life year (LY). These interventions included several testing procedures for transfusion donations (such as viral screening procedures for HIV) and medical procedures (such as autologous blood transfusion in elective surgery and epoietin therapy). Most technologies related to testing and processing blood donations are now standard practice in the USA and Europe. RESULTS: A majority of blood safety interventions had cost-effectiveness ratios greater than $200,000 per QALY or LY. Fewer than 35% had cost-effectiveness ratios less than $50,000 per QALY or LY. CONCLUSIONS: Many blood safety and injury prevention regulations have cost-effectiveness ratios well above $50,000 per QALY. Although $50,000 per QALY is recognized as the standard threshold value against which medical technologies are evaluated, many commonly accepted blood safety interventions and injury prevention measures have much higher cost effectiveness ratios. This indicates that society places a high value on the risks prevented or reduced by such measures and suggests that innovative blood safety technologies should be assessed against a higher cost-effectiveness threshold.