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Objective: To date, there is no clear consensus in the literature which endocrown design with which material is the most effective treatment option to restore endodontically treated maxillary premolars with extensive loss of tooth structure. The aim of this study was to evaluate the stress distribution pattern and failure probability of maxillary first premolars restored with a novel endocrown system compared to the conventional one by means of Finite Element and Weibull analyses., Materials and Methods: Two finite element (FE) models representing two endocrown systems used for restoration of severely-destructed endodontically treated maxillary first premolar tooth were generated: model C for the conventional monolithic IPS e.max CAD endocrown and model P for the novel bi-layered endocrown (PEKKTON ivory coping veneered with cemented IPS e.max CAD). A static occlusal compressive load was axially and centrally-applied. Modified von Mises and maximum principal stress values on the remaining tooth structure, cement lines and restorative materials were evaluated separately. Weibull function was incorporated with FE analysis to calculate the long term failure probability., Results: Regarding stresses occurred in the remaining tooth structure (enamel and dentin), model P transmitted less stresses than model C. The individual enamel of model C showed about 5% and 40% risk of failure at normal and maximum occlusal load values, respectively, while for model P, it had no failure risk at both values. For dentin, model C showed about 13% failure risk at the normal masticatory force, while model P showed only 2%. At clenching value, model C dentin showed about 44% failure risk, while only 9% was resulted for model P., Conclusions: Compared to the conventional endocrown system, the positive impact of the studied novel endocrown system on the stress distribution pattern and also on the survival/failure probability of the restored severely-destructed endodontically treated maxillary first premolar teeth was reflected (more tooth-friendly), not only at normal masticatory forces but also at the maximum functional loads., Clinical Significance: The novel endocrown system using a PEKK coping veneered with cemented IPS e.max CAD can be considered a favorable option for restoration of severely-destructed endodontically treated premolar teeth, with more protection for residual tooth structure. Despite the conventional endocrown system may benefit the durability of tooth bonding, it should not be selected for restoration of clenching cases because of the too high overall failure risk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)