The cyclic resistance of ProTaper Universal (size 25/08) and ProTaper Next (size 25/06) instruments was compared in artificial canals with different curvatures in this study. A total of 30 ProTaper Universal and 30 ProTaper Next instruments were divided into 6 groups (n = 10) and were operated into artificial canals with 3 different angles of curvature (45°, 60°, 90°). The canal length was kept consistent in this study. The number of cycles to fracture (NCF) was counted until file fracture occurred, at which point, the length of the fragment was measured. The data were analyzed statistically using ANOVA complemented by the Tukey test (p < 0.05). Cross sections of the fractured files were scanned by an electron microscope. In the fatigue test, the ProTaper Next displayed more resistance in 45° and 60° canals (p < 0.05), whereas ProTaper Universal exhibited a better operability in 90° canals (p < 0.05). The average length of the fragments from ProTaper Next was significantly shorter than that from ProTaper Universal in 90° canals (p < 0.05). The cross sections of the fractured surfaces became flatter when the curvature angles decreased from 90° to 45°. ProTaper Next was more reliable when shaping in curved canals, whereas ProTaper Universal was more sui for the preparation of root canals with severe curvatures.