[en] Transmissible spongiform encephalopathies, also called prion diseases, represent a family of neurodegenerative disorders that affect various animal species. Since the infectious forms of prions are transmissible and highly resistant to chemical and physical decontamination methods routinely used in healthcare, they represent a challenge for science, medicine, and public health/food systems. Suitable decontamination procedures have been proposed, but they are generally incompatible with the materials from which medical devices are made. In this study, we evaluate a cold gaseous-plasma treatment, based on the outflow from a N2[BOND]O2 microwave discharge, as an alternative decontamination tool against both the non-infectious (PrPC) and infectious (PrPSc) forms of prion proteins. The efficiency of the plasma treatment on these proteins is assessed using an in vitro assay as well as an in vivo bioassay. We showed by Enzyme-Linked Immuno-Sorbent Assay (ELISA) that the N2[BOND]O2 discharge afterglow reduces the immunoreactivity of both non-infectious recombinant and pathogenic prion proteins deposited on polystyrene substrates. Tests done in vivo demonstrate that exposure to the cold-plasma flowing afterglow achieves significant decontamination of stainless steel sutures inoculated with infectious forms of prions to be implanted in mice.