Prions (PrPC) are non-infectious and innocuous proteins which can be found throughout the body, even in healthy humans. However, an abnormal and infectious isoform known as PrPSc exists. This isoform can affect the structure of the brain and lead to neurodegenerative diseases, which are untreatable and fatal. There are several transmission possibilities of PrPSc. Endodontic treatment may transfer PrPSc. Due to their special biologic attributes PrPSc are generally quite resistant towards conventional decontamination treatments and disinfectants. The effect of disinfectants regarding prion decontamination of endodontic instruments is not adequately researched. The aim of this study is to examine the influence of prion decontamination solutions on the cutting efficiency and fracture resistance of nickel-titanium files from the ProTaper system. 300 new Ni-Ti files (ProTaper Universal, Dentsply Maillefer) were utilised in this study. The files were divided into 4 experiment groups (70 files per group) and one control group (20 files). The decontamination procedures were prepared according to the World Health Organization (WHO) and Robert-Koch-Institute (RKI) recommendations. After mechanical and ultrasonic pre-cleaning the files were immersed in 4 different solutions for decontamination: a) 1 M NaOH; b) combination of 2% SDS (sodium dodecyl sulphate) and 0.3% NaOH; c) Hamo 100 PID; d) Prionzyme M. Distilled water was used for the control group. Finally, the specimens were autoclaved. The decontamination process was repeated 7-times consecutively, since according to the manufacturer’s instruction the instruments can be purified several times. Upon completion of the decontamination process the cutting efficiency was measured on a plastic test block. By using an individually manufactured apparatus, the rotating Ni-Ti files were able to carve into the test block. The produced cutting depth was used as the criteria for the cutting efficiency. To detect the fracture resistance an apparatus was used which allowed rotation of the Ni-Ti files in a curved position until these fractured. The number of rotations to fracture of an instrument reflects the fracture resistance. The median cutting depth of the control group amounted to 8,1 mm, whereas the experiment groups totalled up to 6,6 mm (p=0.006). The average number of rotation which lead to a fracture of the files were 189,0 for the control group and 149,3 for the experimental group (p=0.010). The methods and disinfectants for prion decontamination applied in our study are according to the current guidelines and have been repeatedly verified regarding their effectivity. Up to date examinations confirm the potency of additional solutions. It could be shown that a combination of 0.2% SDS, 0.3% NaOH and 20% n-propanol is not only effective against prions, but also against bacteria, spores, virus and fungi. This new combination is a further development of the solution used in our study (0.2% SDS and 0.3% NaOH) and therefore could not be integrated in our investigations. In several comparable studies plastic test blocks were also applied. However, presently there is no standardized set-up. The most reliable method to detect the fracture resistance is by using prefabricated, individually aligned canals according to the file type. This complex method enables nearly consistent file- movements and consequently permits the comparison of different file types. This method was not considered, since the aim of this study is to evaluate the influence of decontamination protocols on Ni-Ti files and not to compare different Ni-Ti files. Considering the results of our study, the daily use of the examined decontamination protocols to disinfect Ni-Ti files can only be limitedly recommended. A reutilization of Ni-Ti files should be desisted due to the theoretical transmission of prions.