Objective: To assess the influence of ormocer, nanofilled, nanoceramic, and microhybrid composite restorative systems on the fracture resistance of maxillary premolars with Class II mesio-occlusodistal (MOD) cavities. Method and Materials: Eighty-four sound maxillary human premolars were divided into six groups of 14 teeth each. Teeth in the first group were left intact and tested as unprepared positive controls. Teeth in the remaining five groups were prepared with MOD cavities. Teeth in one of the five groups were unrestored and tested as negative control. The remaining four groups were restored with an ormocer (Admira), a nanofilled composite (Filtek Supreme), a nanoceramic composite (CeramX mono), and a microhybrid composite (Tetric Ceram). All groups were stored in water at 37°C for 24 hours and thermocycled 500 times between 5°C and 55°C. The specimens were loaded occlusally in a universal testing machine using a metal sphere that contacted only the teeth on the cuspal inclines until fracture occurred. The results were analyzed by Kruskal-Wallis and Mann-Whitney U tests. The level of significance was set at .05. Results: The difference between the mean cuspal fracture resistance of the unprepared positive control teeth and those restored with ormocer, nanofill, and microhybrid composite was found to be statistically significant (P .05). No statistically significant difference in cuspal fracture resistance was found between the unprepared positive control teeth and those teeth restored with nanoceramic composite (P > .05). Conclusion: Under compressive load testing, teeth with microhybrid, ormocer, and nanofilled composite restorations had lower cuspal fracture resistance than those with nanoceramic composite restorations. Keywords: fracture resistance, maxillary premolars, nanoceramic composite, nanofilled composite, ormocer