Aim: To evaluate the influence of different torsional preloads on cyclic fatigue resistance of endodontic rotary instruments made by conventional nickel-titanium (NiTi) or M-Wire. Methods: Eighty new Mtwo (#25/0.06) (Sweden & Martina, Due Carrare, Padova, Italy) and ProTaper Next X2 (Dentsply Maillefer, Ballaigues, Switzerland) were used. The Torque and distortion angles at failure of new instruments (n = 10) were measured and 0% (n = 10), 25%, 50%, and 75% (n = 20) of the mean ultimate torsional strength as preloading condition were applied according to ISO 3630-1 for each brand. The twenty files tested for every extent of preload were subjected to 25 or 50 torsional cycles (n = 10). After torsional preloading, the number of cycles to failure was evaluated in a simulated canal with 608 angle of curvature and 5 mm of radius of curvature. Data were analyzed using 2-way analysis of variance. Scanning electron microscope (SEM) was performed to evaluate the fracture surface of each fragment.Peer review under responsibility of Società Italiana di Endodonzia.