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Aim To investigate the effect of root canal curvature on the failure incidence and fracture mechanism of ProFile rotary Ni-Ti endodontic instruments. Methodology Three hundred mesial root canals of mandibular molars were instrumented using the ProFile system in a crown-down technique up to size 25 0.06 taper. Root canals were classified according to the angle and radius of curvature to: straight (group A: 0 + 10°, radius 0mm), moderately curved (group B: 30 ± 10°, radius 2±1mm) and severely curved (group C: 60±10°, radius 2±1mm). After each use, instruments were cleaned ultrasonically and autoclaved. Instruments that prepared 20 root canals, fractured or were plastically deformed without fracture were retrieved and substituted. Kaplan-Meier estimator was used for survival analysis and post hoc test for determination of significant differences (a=0.05). All fractured instruments were subjected to fractographic analysis under SEM, and all used instruments were viewed under the metallographic microscope. Results Regardless of the size of instrument, fracture and overall failure were significantly more frequent (P |