Background: Rotary Ni-Ti files are susceptible to sudden intra-canal separation due to cyclic fatigue stress, particularly in curved canals. To increase resistance to cyclic fatigue, new heat-treated files have been introduced. This study aimed to compare the performance of four heat-treated Ni-Ti files in two simulated curved root canals by evaluating the effect of the alloy, rotation speed, and diameter of the files on their resistance to cyclic fatigue. Methods: The Ni-Ti files included in the study were the ProTaper Gold® (Dentsply Sirona) F2, ProTaper Ultimate® (Dentsply Sirona) F2, FQ® (Komet) 25.06, and Blueshaper® (Zarc4Endo) Z4 25.06. Two groups of 30 files were selected for each system and were tested in two simulated canals milled in a specific metal template. One group was tested in a 60° curved canal and the other in a 90° curved canal. Results: In the 60° simulated canal, there were no instrument fractures within the 15 min time limit. In the 90° simulated canal, the Blueshaper Z4 demonstrated a lower resistance to cyclic fatigue, while FQ 25.06 showed statistically higher fatigue resistance based on both the Kruskal-Wallis and Games-Howell tests (p < 0.05). Conclusions: No differences were found between files when tested in a 60° curved canal for up to 15 min. However, in a 90° canal, the FQ® files showed significantly higher resistance to cyclic fatigue, especially compared to the Blueshaper® Z4. The ProTaper Ultimate and ProTaper Gold produced intermediate results, with the ProTaper Ultimate F2 slightly outperforming the ProTaper Gold F2.
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