Introduction: The aim of this study was to compare the fracture resistance of upper premolars undergoing root canal treatment that had been temporarily restored with 4 different temporary filling materials. Methods: This study was based on 120 extracted upper premolars. Eight teeth were left intact and served as the negative control group. Mesio-occluso-distal cavities with 2 different designs were prepared for the rest of the teeth (for group 1 a width of one third of the intercuspal distance and for group 2 a width of two thirds of the intercuspal distance). Then, the endodontic access cavities were prepared, and the root canals instrumented with Revo-S rotary files (MicroMega, Besancon, France). Thereafter, a total of 16 teeth consisting of 8 each from group 1 and group 2 served as the positive control group and did not have any temporary filling material. The teeth were randomly divided into 4 subgroups (n = 12) according to the temporary filling material: Cavit G (3M ESPE, St Paul, MN), Coltosol F (ColteneNVhaledent AG, Altstatten, Switzerland), Intermediate Restorative Material (Dentsply Sirona, Konstanz, Germany), or DiaTemp (DiaDent Europe BV, Almere, Netherlands). Each specimen was then subjected to a fracture resistance test using a universal testing machine until the fracture occurred. The force required to fracture each specimen was recorded, and the data were statistically analyzed. Results: The negative control group showed the highest fracture resistance values compared with the other groups, whereas the positive control groups showed the lowest fracture resistance values. There were no statistically significant differences in the fracture resistance of upper premolar teeth undergoing root canal treatment among Cavit G, Intermediate Restorative Material, Coltosol F, and DiaTemp, regard-less of the cavity width (P > .05). Conclusions: The cav-ity design was found to be an effective factor on the fracture resistance of upper premolar teeth undergoing root canal treatment. The temporary filling materials tested did not affect the fracture resistance.