Purpose: To evaluate the fracture resistance and failure modes of endodontically treated mandibular molars restored with different designs of inlays, onlays and endocrowns. Materials and Methods: Extracted mandibular third molars (n = 180) were used. An access cavity was prepared on the occlusal surface of each tooth and the roots were obturated with gutta percha. All specimens were randomly divided into 6 groups (n = 30/group) according to the cavity design and the restoration material used. C: control group without access cavity preparation. IE: MOD inlay preparation with Ev-erX Posterior (GC Europe) in the pulp chamber. IG: MOD inlay preparation with G-aenial Universal Flo (GC America) in the pulp chamber. OE: onlay preparation with EverX Posterior (GC Europe) in the pulp chamber. OG: onlay preparation with G-aenial Universal Flo (GC America) in the pulp chamber. EC: endocrown with an empty pulp chamber. All restorations were fabricated with CAD/CAM system using CERASMART ® (GC Dental products Europe, Belgium) CAD/CAM blocks. Specimens were thermal-cycled and were subjected to a compressive load applied at 30°a ngle relative to the long axis of the tooth with a universal testing machine. Results were statistically analyzed by ANOVA followed by Tukey post hoc tests. Chi-square test and Fisher Exact tests were used for the comparisons among groups.Results: The mean fracture strength was significantly different between the groups (p < 0.001); it was significantly highest for intact teeth, followed by endocrowns (p = 0.021). The strength was significantly lower for inlays (with G-aenial Universal Flo and EverX Posterior), intermediate for onlays with EverX Posterior followed by onlays with G-aenial Universal Flo. Conclusions: Endocrowns exhibited higher fracture resistance than other tested composite resin groups. Endocrowns and onlays showed a more favorable failure mode than inlay restorations.