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The present study was conducted so as to compare the fracture resistanceof roots instrumented with different NiTi rotary file systems in the mesial root canals of maxillary molars. 60 maxillary molars having curvatures of 25°-35° on mesial roots were sectioned below the cementoenamel junction to obtain roots with dimensions of 11 mm in length. They were distributed into 4 groups (n = 15) according to the different instrumentation systems used viz. Group 1: no instrumentation was done, Group 2: Neoendo flex files, Group 3: Protaper universal files, Group 4: Confitaper files. Vertical load was enforced until fracture occurred. Data were statistically analyzed using one-way ANOVA test (P < 0.05). The values for mean load for the control groupwas 420.0±58 Newton (N), for the Neoendo flex group it was 376.5±63 N, for the Protaper universal files group it was 330.0±72 N and for the Confitaper files group it was 399.0±69 N. The differences in fracture load among group 4 and control group was not statistically significant while group 3 showed statistically significant reduction in fracture load.(P > 0.05.) Group 2 showed less reduction in fracture load. Confitaper files lead to minimal reduction in the fracture strength..