This study sought to evaluate how the type of cavity preparation and indirect restorative material affected the fracture resistance of maxillary premolars. Teeth were divided into seven groups (n = 14) according to the cavity preparation design (inlays, partial onlays with palatal canine coverage, and total onlays with coverage of both canines) and restorative material used. After the teeth were prepared, restorations were manufactured using a ceramic or a composite resin and cemented with a resin-based cement, with the exception of a control group consisting of sound premolars with no preparation. Fracture resistance was assessed using a universal testing machine with a 9 mm steel ball at a speed of 0.5 mm/minute until fracture. ANOVA results showed significant differences between restorative materials and types of preparations (p < 0.05). Cavity design did not affect composite resin restorations, while ceramic restorations with partial and total canine coverage presented the lowest fracture resistance values (p < 0.05). Within the limitations of this study, the authors concluded that indirect composite resin restorations offered better performance than ceramic restorations, regardless of the cavity design.