Aim: The aim of this study was to compare the cyclic fatigue resistance of endodontic files of different manufacturers operated in disparate motions. Materials and Methods: Six different brands of nickel–titanium instruments, such as ProFile Vortex™, Vortex Blue™, Twisted File™, HyFlex™, WaveOne™, and S1™ all with a tip size ISO 25 with 0.06 taper, except for WaveOne™ tip size ISO 25 with 0.08 taper, were included in the study. Six groups of 20 rotary files from each system were tested for cyclic fatigue resistance. All files were rotated in a simulated root canal with a certain diameter, angle of curvature, and a radius of curvature of a specific cyclic fatigue testing device until fracture occurred. Time to fracture was recorded for each instrument in each group in seconds. The mean values and standard deviation were then calculated. Data were compared using repeated measures ANOVA for individual comparisons followed by Bonferroni's correction for multiple comparisons. Significance was set at the 95% confidence level. Results: Time of fracture had statistically significant differences among all groups tested (P 0.5). Thus, the S1 file offered a long life span, followed by WaveOne™, ProFile Vortex™, HyFlex™, Twisted Files™, and then Vortex Blue™. Conclusion: The reciprocating instruments (S1 and WaveOne™) had a higher cyclic fatigue resistance than all rotary files used in this study. However, the Profile Vortex (M-wire) and HyFlex (CM) showed better cyclic fatigue resistance than other rotating files in this study. Hence, the blue and R-phase heat treatments did not enhance the cyclic fatigue resistance for rotating instruments.