Introduction: The aim of the present study was to evaluate the cyclic fatigue resistance of the WaveOne Gold Glider (Dentsply Maillefer, Ballaigues, Switzerland), R-Pilot (VDW, Munich, Germany), and ProGlider (Dents ply Maillefer) glide path instruments. Methods: Ten instruments from each glide path system were included in the study. A stainless steel artificial canal with a 90 angle and a 3-mm radius of curvature was used for the testing process. The working lengths of the instruments were fixed at 19 mm, and the instruments were operated using an endodontic motor (X-Smart Plus, Dentsply Maillefer) at recommended setting for each. A digital camera (Sony HDR-XR260; Sony Corporation, Minato, Tokyo, Japan) was positioned on the top of the cyclic fatigue test device, and the time to fracture was recorded in seconds by means of the video camera. For each instrument, the number of cycles to failure was calculated, and the length of the fractured fragment was measured. The data were analyzed using 1-way analysis of variance followed by the post hoc Tukey test. Results: Statistically significant differences in the number of cycles to failure values were observed across the tested groups; the ranking of the instruments was as follows: WaveOne Gold Glider > R Pilot > ProGlider (P < .05). There was no significant difference in the mean length of the fractured fragment of the instruments (P > .05). Conclusions: Within the limitations of the present study, it can be concluded that improved alloy properties and reciprocating motion could enhance the cyclic fatigue resistance of glide path instruments.