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Objective: To evaluate the effect of varying ferrule height and distribution on the fatigue resistance and fracture strength of endodontically treated premolars. Materials and Method: Thirty-two extracted human premolars were endodontically treated and prepared to receive all-ceramic crowns. Teeth were randomly divided into two groups. The occluso-cervical height was reduced to 2 mm and 4 mm for the 1st and 2nd groups, respectively. According to the ferrule distribution, samples in each group were randomly divided into two subgroups with inadequate ferrule on 1 or 2 proximal walls, respectively. Coronal tooth structure was built-up to 4 mm using a core build-up material retained by a fiber post. The CEREC system (Sirona) was used to design and mill lithium-disilicate crowns. All posts and crowns were cemented to their respective teeth using self-adhesive universal resin cement. All crowns were subjected to cyclic loading in a universal testing machine (Instron) (20-100N, 100,000 cycles, 20Hz). After fatigue, crowns were loaded to fracture. Fracture load data were analyzed using two-way ANOVA at a = 0.05. Results: All crowns passed the fatigue testing without any signs of fracture or crack. Two-way ANOVA revealed a statistically significant effect of the number of missing walls (P < 0.05) on the fracture load, but not the ferrule height or the interaction terms. Samples with one missing wall showed higher fracture load in comparison to samples with two missing walls. Conclusion: The number of missing walls, not the ferrule height, has a significant effect on the fracture load of the lithium-disilicate crowns restoring endodontically treated premolars. 2b1af7f3a8