Aim: The aim of this study was to compare the shaping ability of four multi-file systems and one single-file system in simulated S-shaped canals. Materials and methods: Fifty S-shaped canals in resin blocks (Endo Training Bloc S-shape, Dentsply Sirona, Salzburg, Austria) were prepared to an apical size of 25.06 using ProTaper Next (Dentsply Sirona, Ballaigues, Switzerland), HyFlex CM (Coltène/Whaledent, Langenau, Germany), F6 SkyTaper (Komet, Lemgo, Germany), BioRace (FKG Dentaire, La-Chaux-des-Fonds, Switzerland) and Mtwo (VDW, Munich, Germany) systems (n = 10 canals/group). Canal transportation was assessed by comparing the pre-instrumentation and post-instrumentation images under a stereomicroscope. Material removal was measured using a digital template and image analysis software. Deformation of instruments and preparation time were also recorded. The data were statistically analysed by considering the clinical relevance and the ability to maintain the S-shaped form. Results: Canals prepared with HyFlex CM, ProTaper Next and F6 SkyTaper remained better centred compared with those enlarged with the BioRace and Mtwo systems, which removed statistically significantly greater amounts of resin from the inner side of both curvatures (P 0.05). F6 SkyTaper and BioRace were the two fastest systems (P 0.001). No instrument fractures occurred during canal preparation. About 78% of all HyFlex CM files were suitable for reuse. Conclusion: Under the conditions of this study, all five nickel-titanium systems were safe to use. The heat-treated systems HyFlex CM and ProTaper Next maintained the original canal curvature better than instruments made of conventional nickel-titanium. Less tapered instruments at the sequence's beginning had a positive effect on the systems' centring ability. Keywords: CM-wire, M-wire, S-shaped, shaping ability, simulated