Veterinary studies documenting the effect of endodontic treatment on tooth fracture resistance are scarce. The objective of this ex vivo study was to evaluate the effects of mesial access preparation and restoration, as well as pulp chamber access, instrumentation, obturation, and restoration, on the fracture resistance and characteristics of canine teeth in dogs. Sixty-five dog canine teeth were divided into 4 groups: 1. Standard endodontic treatment through a mesial access only; 2. Treatment as per group 1, adding an incisal access, instrumentation and obturation of the pulp chamber, and restoration of the access; 3. Treatment as per group 2, without pulp chamber obturation or restoration of the incisal access; and 4. Untreated teeth. The fracture resistance and characteristics of each group were documented using axial compression testing, angled 45° disto-occlusal to the long axis of the crown. The maximum force prior to fracture in groups 1, 3, and 4 were not statistically different, demonstrating that restored mesial and incisal accesses with pulp chamber instrumentation did not statistically affect fracture resistance. However, obturated and restored group 2 teeth demonstrated decreased fracture resistance compared to all other groups (P < .001). Additionally, 26.7% of group 1 teeth sustained complicated crown fractures, while 100% of group 2 teeth fractured within the obturation or restorative materials, preventing pulp exposure in these cases. Although the cause and clinical importance of decreased tooth fracture resistance following pulp chamber obturation and restoration remains unknown, it may provide protective value for maintaining a coronal seal in the event of tooth fracture.