Aim: The current study compared the fracture resistance of samples instrumented by two rotary files and a reciprocating file, obturated with gutta-percha and AH Plus. Materials and Methods: A total of 60 freshly extracted mandibular premolar teeth with single roots and single canals were acquired and decoronated at or below the cementoenamel junction. The samples were randomly divided into four groups (n = 15). Group 1 control (noninstrumented/obturated), and for Groups 2-4 root canal instrumentation was done by EndoStar E5 (EE5), ProTaper NEXT (PTN), and WaveOne, respectively. Following instrumentation, the samples were obturated using gutta-percha cones and AH Plus sealer using lateral compaction. A week later, vertical load was applied to the specimen's canal in each group until fracture. The loads required for fracture were recorded and statistically analyzed. Results: The mean loads required to fracture (Newton; N) for the four groups were; 388.54 (±29.93), 310.35 (±26.05), 328.40 (±20.67), and 278.54 (±34.16). The loads exhibited highly significant difference (P < 0.0001; analysis variance). The following Tukey's post hoc test confirmed, both samples in Groups 2 and 3 required similar loads for fracture (P > 0.05) and significantly higher than Group 4 (P < 0.01). Conclusion: The samples instrumented by EE5 and PTN exhibit similar fracture resistance. © 2018 Journal of Conservative Dentistry | Published by Wolters Kluwer - Medknow.