Abstract Purpose The present research aimed to assess the impact of endodontic access cavity preparation on the fracture resistance of CAD-CAM crowns. Materials and methods A total of 40 extracted human upper first premolars were utilized in present research. All premolars were affixed in epoxy resin blocks, prepared by utilizing a CNC milling machine to receive full coverage ceramic crowns, and evenly split into two primary groups based on the type of ceramic; Group LD: teeth restored with lithium-disilicate (LD) crowns, and Group PIC: teeth restored with polymer-infiltrated ceramic (PIC) crowns. Every group was subdivided into 2 subgroups (n=10); Subgroup LDI: Intact LD crowns, Subgroup LDR: Repaired LD crowns, Subgroup PICI: Intact vita PIC crowns, and Subgroup PICR: Repaired PIC crowns. Crowns were cemented using Calibra Universal resin cement. The repaired subgroups received a standardized access cavity at the center of the occlusal surface and then repaired with direct composite resin. All samples were exposed to thermo-mechanical loading in a chewing simulator for 118,000 cycles, loaded until failure, and then statistically analyzed. Results For intact control subgroups, the greatest mean scores were showed in PICI (1308.71±244.15 N) compared to LDI (1154.38±133.83 N), and the variation was not statistically significant (P=0.097). For repaired subgroups, the highest mean values were recorded for PICR (727.84±240.52 N) compared to LDR (707.03±298.28 N), and the variation was not statistically significant (P=0.866). Conclusions Both LD and PIC crowns perform the same after exposure to an endodontic access cavity, suggesting their repairability and useability.