Leukoreduction, filtering white blood cells from transfusion blood, effectively avoids leukocyte-related complications of blood transfusion. The technology has proven its relative cost-effectiveness for specific patient populations. With the advent of variant Creutzfeldt-Jakob disease, a transmittable spongiform encephalopathy caused by mad cow disease (bovine spongiform encephalopathy), the hard hit United Kingdom introduced universal leukoreduction for all patients as a precaution for transmission of prions in 1999. This costly policy was followed by many other countries, in the absence of much evidence of an actual health problem or of a more than presumed effectiveness of leukoreduction in preventing prion transmission. The core problem proved to be legal. The blood banks are legally accountable for blood safety. This accountability is absolute, based on avoidance of all possible risks, regardless of costs. This strategy leads to inefficiencies in health care: (i) blood safety management is guided by available rather than cost-effective technology, and (ii) private insurance premiums for civil liability are sharply increasing, while they are in no way related to the expected returns and the high and increasing blood safety. A rational safety policy is to be optimal, taking into account costs and effects of the safety procedures. This issue will need an open discussion with the general public of the real risks and a clear and unambiguous definition of proportionality in the precautionary principle, based on the European law.