This study aimed to compare the fracture toughness of molars with wide mesio-occlusal-distal (MOD) cavities restored with regular and flowable bulk-fill resin composite and a conventional resin composite after 250,000 mechanical cycles of chewing simulation. Thirty-two extracted mandibular third molars were selected and class II MOD cavities involving 2/3 of the intercuspal width and 4 mm depth were prepared. Teeth were divided into four groups based on resin composite type and insertion technique (n=8): (1) CT, unprepared teeth (control); (2) CV, conventional resin composite (Tetric N-Ceram, Ivoclar Vivadent) with incremental technique; (3) R-BF, regular bulk-fill resin composite (Tetric N-Ceram Bulk Fill, Ivoclar Vivadent) with a single increment; and (4) F-BF, flowable bulk-fill resin composite (Tetric N-Flow Bulk Fill, Ivoclar Vivadent) with a single increment, except for a 1-mm-thick layer at the occlusal surface, restored with conventional resin composite (Tetric N-Ceram). All specimens were evaluated to detect the presence and propagation of enamel cracks using a LED transilluminator before and after 250,000 mechanical cycles (SD Mechatronic GmbH). After a chewing simulation, they were subjected to a compressive force in a universal testing machine (DL-2000, EMIC) until fracture. The maximum fracture load of the specimens was measured (N) and the fracture patterns were classified based on the fracture site (above or below the cementoenamel junction [CEJ]). Data were statistically analyzed with oneway ANOVA. All specimens survived after 250,000 mechanical cycles, and no statistically significant differences among groups were observed regarding the fracture toughness (p<0.05). The fracture analysis demonstrated that failures below the CEJ were more common in CV (75%), while CT, R-BF, and F-BF showed this type of failure in 38%, 63%, and 63% of the specimens, respectively. The results of the crack analysis showed that the occurrence of new cracks and crack propagation was also higher in CV (33.3%), followed by R-BF, F-BF, and CT (14%, 14%, and 11% of the specimens, respectively). Teeth restored with regular and flowable bulk-fill composites showed similar fracture toughness after the chewing simulation compared to those restored with the conventional resin composite and unprepared teeth. Furthermore, teeth restored with both regular and flowable bulk-fill composites showed a lower incidence of enamel cracks and fractures below the CEJ compared to those restored with the conventional resin composite.