Objective: The objective of this study was to assess and compare the fracture resistance of roots treated endodontically using WaveOne gold, Reciproc blue, AH plus sealer and GuttaFlow Bioseal sealer. Materials and methods: Total 48 human mandibular premolars with single root were decoronated to a length of 13 mm. The roots were arbitrarily divided into 3 main groups (n=16 each group). Group I control group (roots were instrumented but not obturated), Group II obturated with gutta-percha and GuttaFlow Bioseal sealer and Group III obturated with gutta-percha and AH plus sealer. Each main group was additionally divided into 2 subgroups (n=8 each subgroup) conforming to the system used in root canal preparations, Subgroup A: Reciproc blue system and Subgroup B: WaveOne gold system. All root samples were kept for 1 week at 100% humidity to permit the sealers to set completely. Each sample was then exposed to fracture test utilizing a universal test machine, the data were analyzed statistically with one-way ANOVA test, two-way ANOVA test and Dunnett test (2-sided) at a significant level of 0.05. Results: The results revealed that the highest mean value of fracture resistance was noted in Group IIIB (611.125) followed by Group IIIA (543.250), Group IIB (519.875), Group IIA (511.875), Group IB (270.125) and Group IA (267.875) respectively with statistically highly significant differences among the different groups when compared to the control group. Conclusion: From the results of this study, it seems that the use of AH plus and GuttaFlow Bioseal sealers improved the fracture strength of instrumented roots whereas preparation of the root canals with WaveOne gold and Reciproc blue systems without obturation weakened the tooth structures.