To assess and compare the impact of various computers aided design/manufacturing (CAD/CAM) materials on internal and marginal discrepancies, fracture resistance and failure probability of Endocrown restorations with 3D Finite Element analysis. Forty devitalized human maxillary first molars were collected. After endodontic treatment, they classified into 4 groups (n = 10) based on the materials used for endocrown fabrication. Group V (Vita-Enamic), Group N (Nacera Hybrid), Group T (Translucent Prettau Zirconia) and Group P (Pekkton ivory). All samples were exposed to artificial aging method simulating one year of clinical service. Silicone replica technique and stereomicroscope (25X) utilized to evaluate the marginal and internal gaps of endocrowns at different areas. Fracture resistance test used for cemented specimens followed by qualitative investigation utilizing Stereomicroscopy. Four models representing four endocrown systems used for restoration of severely-damaged endodontically treated upper first molar were generated for finite element analysis (FEA). Axially and centrally static occlusal compressive load was applied. Modified Von Mises and maximum principal stress values on the remaining tooth structure, cement lines and restorative materials were assessed independently. Resulted data were statistically analyzed at P-value ≤ 0.05. In the current study, the highest mean values of internal and marginal discrepancies (μm) among studied groups were reported for Zirconia group (100.300 and 102.650) respectively, while the lowest mean value of internal discrepancy (μm) was observed for Nacera group (69.275) and the lowest mean value of marginal discrepancy (μm) was observed for PEKK group (78.4750). Regarding internal discrepancy, Vita-Enamic and PEKK groups did not exhibit any statistically significant differences (P = 0.293), however zirconia and the other tested groups exhibited statistically significant differences in the mean values of the marginal gap region (p 0.05).On the other hand, PEKK group showed the highest mean value of fracture resistance (1845.20 N) and the lowest value was observed for Vita-Enamic group (946.50 N). Regarding to stress distributions through 3D FEA, and according to modified von Mises (mvM) analysis, the greatest possible stress values were noticed in PEKK model in relation to tooth structure, cement line, and flowable composite as the following: (93.1, 64.5, 58.4 MPa) respectively, while Zirconia revealed lower maximum stress values (11.4, 13.6, 11.6 MPa) respectively. Statistically excellent marginal and internal fit was observed for PEKK in relation to other used endocrown materials. Also, PEKK material explained fracture resistance comparable to zirconia value while the lowest value was detected for Vita Enamic material.