Introduction: The goal of this study was to compare the impact of NaOCl, EDTA, and chitosan on the cyclic fatigue of 2Shape, HyFlex EDM, and RACE EVO. Methods: A total of 120 new 2Shape (n=40), HyFlex EDM (n=40), and RACE EVO (n=40) files were subdivided randomly into four groups (n=10): Group (A) with no immersion, Group (B) with immersion in 5.25% NaOCl for 5 min, Group (C) with immersion in 17% EDTA for 5 min, and Group (D) with immersion in 0.2% chitosan for 5 min. The files were rotated in an artificial canal with a 5mm radius and a 60° curvature at body temperature until they fractured, and the number of cycles to fracture was measured. ANOVA test and Tukey post-hoc test were used to analyze the data. Results: Immersion of the files in NaOCl, EDTA, or chitosan solutions had no significant effect on the number of cycles to fracture (P > 0.05). Conclusion: The irrigation solutions did not have any influence on the cyclic fatigue of the tested files. [ABSTRACT FROM AUTHOR]