Aim: The purpose of this study was to evaluate the effect of the angle and radius of root canal curvature on the resistance to cyclic fatigue of ProTaper Next (Dentsply Maillefer, Ballaigues, Switzerland) and NRT (Mani, Toshigi-Ken, Japan) rotary nickel-titanium instruments. Methods: One hundred and sixty files were rotated until fracture in simulated canals of 60° and 45° angles of curvature with two different radii (5.0 and 2.5 mm), using a custom-made testing platform. The number of cycles to failure (NCF) was calculated and statistical analysis was carried out using three-way analysis of variance (ANOVA) (P ≤ 0.05) and Bonferroni's post-hoc test. Scanning electron microscope analysis was done to assess fractured files. Results: The NRT system showed a higher mean NCF when compared to ProTaper Next, when the angle of curvature was 60° or 45° in both 5.0 mm and 2.5 mm radii. Statistically significant differences were found between the NCF mean values of NRT and ProTaper Next, when the radius was 5.0 mm, however no significant differences were found when the radius was 2.5 mm. Conclusions: It was concluded that when the angle of root canal curvature increased and the radius decreased, the cyclic fatigue resistance of NRT and ProTaper Next files decreased. Keywords: Cyclic fatique, NRT, ProTaper Next