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The objective of this study was to compare the shaping efficacy of 5 Ni-Ti rotary instruments with different cross-sectional designs in simulated S-shaped resin root canals.One hundred canals (n = 20) were instrumented to apical size 0.04/25 with ProFile, K3, NiTi-TEE, EndoWave, or HeroShaper. Pre- and postoperative images were superimposed. Width of resin removal was measured. Total amount of material removal, amount and direction of transportation, and centering ratios were determined. Data were analyzed using 1-way ANOVA and post hoc Tukey and Newman-Keuls multiple comparison tests.In terms of centering ratio and amount of transportation, ProFile followed by K3 gave the best results almost throughout the whole canal. However, ProFile created insufficient taper. Canals instrumented with the other 3 systems were transported and lacked flow.The K3 system, probably owing to its cross-sectional design and sequence encompassing a high number of instruments, seems under the conditions of this study to be a better choice in preparing S-shaped simulated root canals.