The aim of this study was to evaluate the effect of cavity design and glass fiber posts on stress distributions and fracture resistance of endodontically treated premolars. Fifty extracted intact mandibular premolars were divided into 5 groups (n = 10): ST, sound teeth (control); MOD, mesio-occlusal-distal preparation + endodontic treatment (ET) + composite resin restoration (CR); MODP, mesio-occlusal-distal + ET + glass fiber post + CR; MOD2/3, mesio-occlusal-distal + two thirds occlusal-cervical cusp loss + ET + CR; and MODP2/3, mesio-occlusal-distal + two thirds cusp loss + ET + glass fiber post + CR. The specimens were loaded on a cusp slope until fracture. Fracture patterns were classified according to four failure types. Stress distributions were evaluated for each group in a two-dimensional finite element analysis. The fracture resistance of the MODP, MOD2/3, and MODP2/3 groups was significantly lower than the ST and MOD groups (p < 0.05). The loss of dental structure and the presence of fiber post restoration reduced fracture resistance and created higher stress concentrations in the tooth-restoration complex. However, when there was a large loss of dental structure (MODP2/3), the post reduced the incidence of catastrophic fracture types.