Background. In order to support the economic and financial sustainability of the Italian health system, there is a need to define technically and economically efficient strategies that assure the self-sufficient apheretic production of plasma. Material and methods. Process and product costs at the Casa del Donatore (CD) in Bologna were determined on the basis of costing models used at Verona's Inter-hospital Department of Transfusional Medicine (IDTM) by academics from the University of Turin and those used at the Marche Regional IDTM by academics from Marche Polytechnic University. During the first phase, data was collected concerning donors, biological screening tests, the number of units produced/discarded, the materials used (individual pharmacy codes and related final expenditure), human resources (number, professional status, time involved, the number of activities per day, percentage productivity), equipment, and general costs. During the second phase, direct costs were verified and the costs common to the units produced were attributed using the functional principle. Results. The overall cost of a litre of plasma collected by means of apherisis (about \u20ac 280) was similar at the three centres, but there were differences in their cost structures that could be attributed to organisational choices, economic factors and/or structural variables. Plasmapheresis accounts for 24% of the plasma collected in Marche and the CD, but 17% of that collected in Verona, whereas the donation index is lower in the CD (1.8) than in the other two centres (2.2). The annual donor screening tests are substantially similar, but there are some differences in their timing (at the time of screening candidate donors or at the time of first donation). There are also some differences in the use of tests that are not required by law but are carried out in order to protect donors and recipients. The working times in three centres are similar, but personnel costs vary because of their different retribution policies. Discussion. Comparing the cost determinants at each centre made it possible to highlight changes that each can make in order to improve efficiency, and may lay the basis for doing the same in other organisational contexts