This study evaluated the fracture resistance of endodontically treated teeth restored with different base materials and mesio-occlusal-distal (MOD) ceramic inlays. Fifty mandibular molars were assigned into five groups (n=10 per group). Group1 (control) comprised intact molar teeth without any treatment. Teeth in other groups were subjected to root canal treatment and restored with MOD ceramic inlays on different base materials. In Group 2, base material was zinc phosphate cement; Group 3's was glass ionomer cement; Group 4's was composite resin, and Group 5's was composite resin reinforced with fiber. Finally, a continuous occlusal load was applied until fracture occurred. Mean fracture resistance of Group 1 (3,027 N) was significantly higher than the other groups (890, 1,070, 1,670, 1,226 N respectively). Fracture resistance of Group 4 was statistically comparable with Group 5 and significantly higher than Groups 2 and 3 (p<0.05; Tukey's HSD). Use of different base materials under ceramic inlay restorations could affect the fracture resistance of endodontically treated teeth.