This study aimed to assess the influence of different cross-sectional area on the cyclic fatigue fracture of Ni-Ti rotary files using a fatigue tester incorporating cyclical axial movement. Six brands of Ni-Ti rotary files (ISO 30 size with .04 taper) of 10 each were tested: Alpha system (KOMET), HeroShaper (MicroMega), K3 (SybronEndo), Mtwo (VDW), NRT (Mani), and ProFile (Dentsply). A fatigue-tester (Denbotix) was designed to allow cyclic tension and compressive stress on the tip of the instrument. Each file was mounted on a torque controlled motor (Aseptico) using a 1:20 reduction contra-angle and was rotated at 300 rpm with a continuous, 6 mm axial oscillating motion inside an artificial steel canal. The canal had a 60° angle and a 5 mm radius of curvature. Instrument fracture was visually detected and the time until fracture was recorded by a digital stop watch. The data were analyzed statistically. Fractographic analysis of all fractured surfaces was performed to determine the fracture modes using a scanning electron microscope. Cross-sectional area at 3 mm from the tip of 3 unused Ni-Ti instruments for each group was calculated using Image-Pro Plus (Imagej 1.34n, NIH). Results showed that NRT and ProFile had significantly longer time to fracture compared to the other groups (p < .05). The cross-sectional area was not significantly associated with fatigue resistance. Fractographycally, all fractured surfaces demonstrated a combination of ductile and brittle fracture. In conclusion, there was no significant relationship between fatigue resistance and the cross-sectional area of Ni-Ti instruments under experimental conditions.