To evaluate the influence of retainer design and ceramic materials on the durability of minimally invasive cantilever resin-bonded fixed dental prostheses (RBFDPs) after artificial aging.One hundred caries-free human mandibular molars were prepared as abutments for all-ceramic cantilevered fixed dental prostheses using the following retainer designs: One wing (OW), Two wings (TW), Inlay ring (IR), Lingual coverage (LC), and Occlusal coverage (OC). Two ceramic materials were used: monolithic high translucent zirconia(z) and zirconia-reinforced lithium disilicate (ZLS2) (n=10). All restorations were adhesively bonded with resin cement. The thermocycling of the specimens were performed between 5°C and 55°C for 10,000 cycles and then exposed to 240.000 cycles of dynamic loading on a chewing simulator. All surviving specimens were loaded onto the pontic until failure using a universal testing machine.The mean failure load ranged from 124.00 to 627.00 N for the zirconia groups and from 133.30 to 230.00 N for the ZLS2 groups. Regarding the materials, a significantly higher failure load was recorded in the zirconia groups than in the ZLS2 groups (P<0.001), except for OW (P=0.748). Regarding the retainer designs, a significant different failure load was recorded between the different designs except for IR and LC in the zirconia groups, IR and OC, OW and TW, and TW and LC in the ZLS2 groups (P<0.001).Zirconia IR, LC, and OC can be used as cantilever RBFDP in the premolar region. The fracture resistance of the ZLS2 design was below the normal bite force and should not be recommended as the first option.