Abstract : <p>The NiTi file systems have been launched to dentistry to reduce the chance of endodontic treatment errors. But there is a combining issue, the risk of instrument fracture, mainly due to cyclic fatigue during rotation within a curved canal. This study aimed to compare the cyclic fatigue resistances of Hyflex EDM [Coltene], EdgeOne Fie [EdgeEndo] and One Curve [Micro Mega] instruments at different levels of canal curvature. A total of 60 new files [size 25] divided into three groups and then each group divided into two subgroups, subjected to fatigue tests in two simulated canals with different curvature location, apical [n=10] and middle [n=10]. All instruments were rotated until failure and the number of cycles to failure [NCF] and fragment length[FL] was registered. The results showed that the NCF of all groups were lower in middle curved canal compared to the apical curved canal (P &lt; 0.05). In the apical curved canal, no significant differences in NCF observed between the EO and HEDM files (P &gt; 0.05) but OC files showed a lower significant than others (P &lt; 0.05). In the middle curved canal, no significant difference NCF observed between EO and OC files (P &gt; 0.05), but HEDM showed a lower significant than others (P &lt; 0.05). No statistical difference in the FL among instruments. Concluding that EO Fire instruments had higher resistant to cyclic fatigue, but without significant difference with HEDM at the apical level and without significant difference with OC at the middle level</p>