Objectives: The aim of this study was to evaluate the fracture resistance of endodontically treated teeth restored with nanohybrid resin composite versus nanofilled resin composite indirect inlay systems with and without cyclic loading.Methods: A total of 60 non-carious human maxillary first premolar teeth were selected. The teeth where divided into three main groups according the restoration material whether Grandioso, Ceram.xone or Filtek™ Z350XT. Each group was further divided into two subgroups according to cyclic loading application. All teeth were endodontically treated and standardized MOD cavities were prepared and the teeth then were restored. Half of the specimens were subjected to cyclic loading and then all samples were individually mounted on a universal testing and fracture test was done. A Three-way ANOVA, followed by Tukey’s post-hoc test was used.Results: Grandioso nanohybrid resin composite showed the highest fracture resistance followed by nanohybrid resin composite Ceram. X one and nanofilled resin composite Filtek™ Z350XT respectively. Conclusion: The type of resin composite greatly influences the fracture resistance of MOD inlay used for restoring endodontically treated teeth.