To examine the fracture resistance and fracture modes of endodontically treated teeth (ETT) restored using onlays of different materials fabricated using computer-aided design and computer-aided manufacturing (CAD-CAM). Methods: Sixty maxillary first premolars were randomly assigned to six groups (n=10). The first group comprised intact teeth (INT). The remaining premolars were prepared for mesio-occluso-distal cavity and root canal treatments. Group 2 was treated using polymer-reinforced zinc oxide-eugenol intermediate restorative material (IRM). Groups 3−6 were core build-up, prepared for onlay, and restored using resin nanoceramic (Cerasmart [CER]), polymer-infiltrated ceramic networks (Vita Enamic [VE]), lithium disilicate-based ceramic (IPS e.max CAD [EM]), or translucent zirconia (Katana Zirconia UTML [KZ]). All specimens were immersed in 37 °C distilled water for 24 h. Each specimen was loaded at 45° to the long axis until failure (crosshead speed, 0.5 mm/min). Fracture loads were analyzed using one-way analysis of variance and Tukey's post-hoc test (α=0.05). Results: There were no significant differences in fracture load among the INT, CER, VE, and EM groups. The fracture load in the KZ group was significantly higher than those in the other groups (P < 0.05). Fracture load was the lowest in the IRM group (P < 0.05). The unrestorable failure rate was 70% in the KZ group and 10−30% in the other experimental groups. Conclusions: ETT restored using Cerasmart, Vita Enamic, or IPS e.max CAD onlays had fracture resistance and patterns comparable to those of intact teeth. Katana Zirconia UTML-restored ETT had the highest fracture load but also a higher unrestorable failure rate.