The purpose of the present study is to evaluate the fracture resistance of endodontically treated maxillary premolars restored using CAD/CAM onlays or crowns and luted with two types of resin cement. Forty all-ceramic crowns and twenty onlays were fabricated on maxillary premolars using the Cerec 3 system (n=10). The abutments were randomly subjected to two different procedures: Endodontic treatment was performed on forty teeth restored through a mesio-occlusal-distal (MOD) cavity preparation with composite resin fillings; twenty teeth without endodontic treatment served as control. In endodontically treated teeth restored using IPS e.max CAD crowns or onlays, the fracture loads were lower than those of the control. Endodontic treatment of teeth restored using CAD/CAM crowns does not impair the fracture load but shows more severe fractures than teeth restored using CAD/CAM onlays. This suggests that a CAD/CAM onlay might be an effective method for the restoration of endodontically treated premolars with MOD cavity defect.