Background: During various sterilization procedures of NiTi instruments adversely affect their fracture resistance due to surface corrosion or roughness making them vulnerable to cyclic fatigue. Aim: To evaluate the resistance to cyclic fatigue from repeated cleaning and sterilization procedures on corrosion of NiTi rotary files under various concentrations of Sodium Hypochlorite (NaOCl) and autoclave sterilization. Materials and methods: A total of 60 NiTi files (ProTaper S1) divided into 6 groups (n=10) according to the environment in which the cyclic fatigue test was to be studied were subjected to different methods of sterilization involving autoclaving at 121°C and immersion in 1% NaOCl and 5.25% NaOCl in this study using root canal models (Curved canal, DENTSPLY, USA) simulating a curved root canal. Endodontic rotary files (ProTaper S1) not exceeding 16 mm intracanal length was used under the specified irrigating solutions and repeated till the rotary file fractured. The number of cycles needed for instrument fracture (NCF) was calculated and the NiTi files in each group were further examined under SEM with EDX analysis (S-3500N, Hitachi, USA) for topographical analysis. Results: A statistically significant reduction in the lifetime of the NiTi rotary files was observed with an increase in number of cycles of autoclave sterilization files and increasing concentrations of NaOCl and when used in combination of both autoclave and chemical sterilization. The topographic analysis of the fractured files in all groups exhibited classical signs of fatigue fracture. Conclusion: Clinicians should judiciously use these instruments with respect to repeated and multiple use of instruments that make them vulnerable to cyclic fatigue/fatigue failure rendering these instruments susceptible to fracture within the root canal anatomy leading to otherwise avoidable complications possibly due to cumulative surface corrosion or roughness.