Statement of problem: Different preparation designs and materials used for endocrown manufacturing are important factors for the success of the restoration, but the studies that evaluated the effect of the designs and materials on the fracture resistance are inadequate. Purpose: This study evaluated the fracture resistance of endocrowns with two preparation designs and manufactured with two CAD/CAM ceramic materials. Materials and Methods: Forty endodontically treated maxillary 1^st molar teeth were prepared to receive endocrown restorations and divided into two main groups according to the preparation designs: Group B (n=20) endocrowns with butt joint design; Group F (n=20) endocrowns with ferrule design. The main groups were subdivided into two subgroups according to the CAD/CAM material used: Subgroup E (n=20) endocrowns manufactured from lithium disilicate glass ceramic (LD) (IPS e.max CAD, Ivoclar-Vivadent, Liechtenstein); Subgroup C (n=20) endocrowns manufactured from hybrid nano-ceramic (HN) (Cerasmart 270, GC, Japan). The endocrown restoration were cemented to the prepared teeth using dual cured self-adhesive resin cement. The specimens were subjected to thermal aging up to 10.000 cycles in a thermocycling paths with 5^oC and 55^oC. All specimens were subjected to a compressive force until fracture occur by using universal testing machine. The maximum compressive force was recorded for all specimen; then the failure modes were examined using scanning electron microscope SEM. Results: The mean value of fracture resistance of BC group was statistically and significantly higher than the other tested groups; (BC group, 4361.01±554.32 N) and the lowest mean value was recorded with FE group (2693.04±638.69 N). B Group showed significant higher fracture resistance than F Group (B group, 3707.09±1156.06 N; F group, 2724.34±601.96 N). C subgroup showed significant higher fracture resistance compared to that of E subgroup (C subgroups, 3558.33±995.92 N; E subgroups, 2873.10±983.95 N). All groups showed a high rate of catastrophic failures but at loads greater than normal maximum masticatory forces. Conclusions: Butt joint design endocrowns exhibited significantly higher fracture resistance than ferrule design endocrowns. Hybrid nano-ceramic endocrowns showed higher fracture resistance than lithium disilicate endocrowns. Endocrown showed a high percent of irreparable failure mode but at loads larger than normal masticatory function.