(1) Background: The failure of nickel–titanium (NiTi) rotary files is a complication related to endodontic instruments. The aim of this study was to compare the resistance to cyclic fatigue between rotary and reciprocating file systems. (2) Methods: Specific PICO: Population (P): artificial root canals; Interventions (I): instrumentation with NiTi rotary and reciprocating files; Comparison (C): rotary versus reciprocating files; Outcome (O): cyclic fatigue resistance. Studies were identified through bibliographic research using electronic databases (Medline, Embase, Scopus, SciELO, and WOS). The studies were combined using a random effects model by the inverse variance method. The effect size was the mean of the time to fracture (TTF) and number of cycles to fracture (NCF). Heterogeneity was assessed using the p value of the Q test for heterogeneity and the I2. (3) Results: TTF for rotary files was determined in 474.5 s and 839.1 for reciprocating without statistically significant differences. NCF for rotary systems was determined in 1444.2 and for reciprocating file systems in 4155.9 with statistically significant differences (p = 0.035), making reciprocating files more resistant. (4) Conclusions: Reciprocating files have better resistance to cyclic fatigue than rotary files. When tested in double curvature canals, reciprocating files also showed higher resistance.
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