Introduction: The purpose of this article was to compare the cyclic fatigue resistance of Reciproc and Reciproc Blue files (VDW GmbH, Munich, Germany) that were used to prepare root canals of mandibular molar teeth with or without a glide path. Methods: Sixty Reciproc R25 and 60 Reciproc Blue R25 files were used. The Reciproc and Reciproc Blue groups were divided into 3 subgroups (ie, as received condition, used without a glide path, and used with a glide path). All the instruments were rotated in a stainless steel artificial canal with an inner diameter of 1.5 mm, a 60 angle of curvature, and a radius of curvature of 5 mm until fracture occurred. The number of cycle to fracture was calculated, and the length of the fractured segments was measured. The Kruskal-Wallis test was performed to statistically analyze the data using SPSS 21.0 software (IBM Corp, Armonk, NY) at a 5% significance level. Results: The cyclic fatigue resistance of as received condition Reciproc Blue files was found to be higher than as received condition Reciproc files (P < .05). Reciproc Blue files used for root canal preparation showed higher cyclic fatigue resistance than Reciproc files used for root canal preparation (P < .05). There was no statistically significant difference between Reciproc and Reciproc Blue files used with a glide path and without a glide path (P > .05). There was no statistically significant difference in the mean length of the fractured fragments of the instruments (P > .05). Conclusions: Within the limitations of this in vitro study, it was concluded that creating a glide path using ProGlider files had no effect on the cyclic fatigue resistance of RPC and RPC Blue files.