The aim of this study was to investigate whether cyclic fatigue resistance is increased for Controlled Memory (CM) Nickel-Titanium (NiTi) instruments, compared to instruments produced using traditional NiTi and instruments produced using M-Wire alloy. Two groups of NiTi endodontic instruments consisting of identical instrument sizes (constant 0.06 taper and 0.25 tip diameter and constant 0.04 taper and 0.40 tip diameter) were tested: group A compared Hyflex™ CM, Vortex ™ and ProFile ™ size 25 and 0.06 taper and group B compared Hyflex™ CM, Vortex™ and ProFile™ size 40 and 0.04 taper. 10 files from each different subgroup were tested for cyclic fatigue resistance. Mean and standard deviations of the Number of Cycles to Failure (NCF) were calculated for each group and data were statistically analysed (p < 0.05). Hyflex™ CM instruments, size 25 and 0.06 taper, and size 40 and 0.04 taper, showed a significant increase in the mean number of cycles to failure when compared with size 25 and 0.06 taper Vortex™ and ProFile™. No statistically significant difference (p > 0.05) was noted between Vortex™ and ProFile™ in the tested sizes. The new manufacturing process involving memory shape heat treatment produced new NiTi rotary files (Hyflex™ CM) significantly more resistant to fatigue than instruments produced with other proprietary methods of treatment (Vortex™) and with the traditional NiTi grinding process (ProFile™).