PurposeIn metal-ceramic restorations, the substructure fabrication method and design may affect the prognosis of the prosthesis. This study evaluated and compared the fracture resistance of metal-ceramic restorations fabricated with different substructure fabrication methods using two different alloy powders and designs.Materials and MethodsTitanium abutments prepared for maxillary central incisor specimens were divided according to the substructure fabrication method (CAS, casting; SLM, selective laser melting), alloy powder type (SLM1, higher Cr and Mo contents; SLM2, control), and substructure design (A, covering one-third of the palatal surface; B, covering two-thirds). Six groups (n = 10 per group) were prepared for fracture resistance analysis. Following surface air particle abrasion of the substructures, their surface morphologies were observed, and the surface roughness was measured. After ceramic veneering, cementation to a titanium abutment, and water storage (24 h), thermomechanical aging was performed. The fracture load was measured, failure mode analysis was performed, and the ceramic-substructure interface was observed. Statistical analysis was also performed.ResultsThe surface roughness was higher in the CAS group (compared to SLM1 and SLM2 groups), indicating that the fabrication method affected the fracture resistance. The substructure design and alloy powder composition had no effect. No surface roughness and fracture resistance differences were observed between the SLM1 and SLM2 groups. The most common fracture pattern was cervical ceramic fracture. No differences in fracture mode were observed between groups.ConclusionsThe fabrication method affected the fracture resistance, with SLM leading to a higher resistance. The substructure design had no effect on the fracture resistance.