The present study was conducted to compare the resistance tocyclic fatigue of two Nickel-Titanium rotary instruments; TwistedFiles (SybronEndo) and RaCe (FKG Dentaire) before and afterbeing used in 4 and 12 canals. Methodology: Sixty Nickel-Titanium endodontic files were tested for cyclic fatigue. Theseinstruments consisted of two main groups; Twisted, and RaCefiles, in which both represented equilateral triangular cross section,and identical instrument sizes; 0.25 tip diameter and .04 taper.Each group was divided into 2 sub-groups; un-instrumented subgroupand instrumented sub-group. The un-instrumented sub-groupwas tested directly on a costume made cyclic fatigue testing devicewith an artificial canal having a curvature of 45° and 5mm radius.It was rotated in the device till fracture occurred and the time wasrecorded and converted to number of cycles. The instrumentedsub-group was further divided each into 2 groups which were usedto prepare 4 and 12 canals of natural teeth before it were tested onthe cyclic fatigue testing device. Results: Applying t and ANOVAtests to the collected data the following results were obtained; theun-instrumented groups showed highest statistically significantnumber of cycles to failure followed by the groups used to preparefour canals, and the groups used to prepare twelve canals showedthe lowest number. All the groups showed same length of thefractured part of the files. Conclusion: prolonged use of rotaryNickel-Titanium files decrease resistance to cyclic fatigue. Theinstrument manufacturing method has an impacting effect onflexural cyclic fatigue. The twisting manufacturing procedure usedfor Twisted files proved to be better than the grindingmanufacturing procedure used for RaCe files.