Plasma-based sterilization is a promising alternative to ethylene oxide (EO) for reprocessing of electrophysiology catheters. To assess its safety in terms of material damage, modifications of surface and bulk properties as well as hydrolytic stability of sterilized catheters were evaluated. Polyurethane (PU) single-use electrophysiology catheters were subjected to one, five, and ten sterilization cycles by Sterrad-100S and Plazlyte, as well as by pure EO for comparison. Surface analysis techniques (ATR-FTIR, XPS, DCA) showed oxidation limited to the near-surface layer induced by both plasma-based sterilizers, whereas EO induced slight but deeper alkylation. Using bulk analysis techniques (RP-HPLC, SEC), oligomer alteration was observed after all three sterilization techniques, without modification of molecular weights. Hydrolytic stability of catheters was slightly changed by plasma-based sterilization, with a small increase in released oligomers. Finally, although Plazlyte and Sterrad are both plasma-based techniques, they induced different impacts on catheters, such as the degradation of an additive with Sterrad, and a clear difference in coloration with Plazlyte.