New designs and processing of Niquel-Titanium (NiTi) have been introduced to increase resistance to cyclic fatigue. The purpose of this study was to compare the cyclic fatigue resistance of 3 NiTi rotary instruments, ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland), Profile Vortex Blue (PVB; Dentsply Tulsa Dental, Tulsa, OK, USA) and ProTaper Universal (PTU; Dentsply Maillefer, Ballaigues, Switzerland). A cyclic fatigue test was conducted operating instruments from ProTaper Next X2, Profile Vortex Blue 25.06 and ProTaper F2. A total of 234 instruments were rotated in 2 simulated stainless steel curved canals with different angles of curvature (45º and 60°) and 5-mm radius of curvature. The number of cycles to fracture (NCF) was calculated. Data were compared using 2-way analysis of variance and post-hoc Bonferroni test in software (SPSS 15.0, Chicago, IL). Statistical significance was set at P<0.05. Profile Vortex Blue showed higher resistance to cyclic fatigue in both curved canals than ProTaper Next and ProTaper Universal (P<0.001). ProTaper Universal obtained the lowest resistance to cyclic fatigue in both canals (P<0.001). Profile Vortex Blue was the most resistant to cyclic fatigue failure, followed by ProTaper Next and ProTaper Universal. Anatomical complexity (angle of curvature) and manufacturing process of NiTi are important factors for resistance to cyclic fatigue.