Purpose: The aim of the present study was to compare the fracture resistance of endodontically treated maxillary premolars with mesio-occlusodistal (MOD) cavities restored using various restorative materials and luting agents. Materials and Methods: Eighty extracted human maxillary premolars satisfying certain predetermined criteria were subjected to seven different restoration methods (10 premolars per method). After endodontic treatment, an MOD cavity was prepared in each specimen, and restoration was carried out by one of the following methods: group 1 = control (intact premolars); groups 2 and 3 = restoration using a photo-cure resin composite with and without bonding, respectively; groups 4 and 5 = restoration using a cast-metal inlay with zinc phosphate and adhesive resin cements, respectively; groups 6 and 7 = restoration using a cast-metal onlay with zinc phosphate and adhesive resin cements, respectively; and group 8 = restoration using a hybrid resin onlay. A fracture test was conducted to determine the fracture resistance and fracture mode of each specimen. Results: Fracture resistance was greatest for teeth restored using a cast-metal onlay cemented with adhesive resin cement, but those fractures that did occur were generally unrestorable. Fracture resistance of teeth restored using a cast-metal inlay was also high. Fracture resistance for teeth restored using a resin composite was significantly lower, but the majority of these fractures were restorable. Conclusion: Endodontically treated maxillary premolars with MOD cavities could be successfully restored by cast onlay and inlay restorations luted with adhesive resin cement, but their failure mode was often unfavorable. Int J Prosthodont 2004;17:94–98.