Prions are a novel class of infectious agents that cause subacute encephalopathy in man and animals as human Creutzfeldt-Jakob disease (CJD), sheep scrapie and bovine spongiform encephalopathy (BSE). Previously, prions were shown to be transmitted by neuro- and ophthalmosurgical measures and by application of brain-derived therapeutic hormones. Recently, prions have been detected in blood specimens of experimentally infected monkeys indicating a principal threat to transfusion medicine, furthermore in human or bovine materials used in reconstructive surgery. In this article the risk of prion transmission from the surgeon to the patient or vice versa during (orthopedic) surgery is reevaluated including the issues of blood transfusion. This is accomplished based on recent epidemiologic findings and biometric calculations on the spread of prions in animals and humans as well as in terms of experimental data on artificially contaminated medical materials and devices. The overall risk of prion transmission in orthopedic surgery is considered very low if adequately prepared and sterilized materials and devices are used.