This study investigated whether filtration of leucodepleted red cells in SAG-M through the P-CAPT™ filter in order to prevent the potential risk of vCJD infection associated with prion transmission through transfusion has any deleterious effect on red-cell quality. Bottom-and-top SAG-M leucodepleted red-cell concentrates (24 units) were prion-reduction filtered on the day following collection, with half of the units undergoing irradiation on day 14. A control group (12 units) was not prion filtered. Units were sampled at 7-day intervals up to day 35 and tested using standard measures of red-cell quality as well as prothrombin content (to examine prion filter efficacy). Haemoglobin loss per unit was ∼9 g and in some cases levels were below standard specification (40 g). Haemolysis increased significantly after filtration [0.01 (0.00-0.05) vs. 0.23 (0.07-0.52, p<0.001)]. Prothrombin levels were reduced 41.6-fold compared to leucodepleted red-cell units. Product specifications were within or close to routine acceptable levels. Owing to the reduction in haemoglobin levels below those specified, it may be preferable to reduce haemoglobin specification levels and transfuse more prion-filtered units rather than transfuse potentially unsafe blood product. The risk of transfusing more units with less haemoglobin should be offset against the risk of transfusing unfiltered blood.