Non-A non-B hepatitis is the most common serious sequela of blood transfusion, and its screening has become an essential goal of blood transfusion centers. Before 1989, two surrogate screening tests (for alanine aminotransferase and for antibody to hepatitis B core antigen) were used; in 1989, a direct test for the antibody to hepatitis C virus (the main agent of this hepatitis) was developed. The French National Agency for the Development of Medical Evaluation undertook an investigation to determine the optimal prevention strategy for posttransfusion non-A and non-B hepatitis (PTH). A detailed literature review was performed, complemented by expert group opinion. The performance of each test was derived indirectly by calculating the number of cases of PTH averted by each test. Hepatitis C virus testing is probably the most promising strategy, but different policies can be developed given the uncertainties of scientific data. Cost considerations should be taken into account in identifying the best screening strategy.