Despite significant technological advancements in the characteristics and shape of nickel-titanium (NiTi) files, fracture can still happen while they are being used. This study aimed to compare the resistance to cyclic fatigue of two different endodontic rotary file systems. Material and Method: In present in-vitro study 40 rotating NiTi files in total, separated into two groups: group I (Protaper Next, Dentsply) and group II (NeoEndo Flex, Orikam Healthcare India Private Limited). The institutional ethical review board gave the study its approval. The length, 6% taper, and ISO size of rotary files were maintained as standards. All of these files underwent testing in a model made equipment with a radius of curvature of 5 mm and an angle of curvature of 60°. Every file was inserted into the Dentsply X smart and rotated at 400 rpm and 2.5 N/cm torque. Time until the file fractured was noted. Number of cycles performed by a file until fracture was calculated as no. of cycles performed by experimental file until fracture = 400/60 x Time taken till fracture was recorded. Result: The NCF values were highest for protaper next file (905 ± 84.31) and least cyclic resistance was observed with Neo Endo Flex files (645 ± 41.51). Conclusion: Cyclic flexural fatigue resistance was observed highest for protaper next group and lowest for Neoendo group.