OBJECTIVE: To investigate the effect of cervical margin relocation with four different injectable restorative materials on the fracture resistance of molars receiving mesio-occluso-distal CAD/CAM nanoceramic onlay restorations. MATERIALS AND METHODS: One hundred and five sound mandibular molars received a standardized mesio-occluso-distal onlay preparation, with cervical margins located 2 mm apical to the cemento-enamel junction. The molars were randomly allocated into five groups (n = 21) according to the cervical relocating materials used: Group I had no cervical margin relocation
Group II used a highly viscous glass ionomer
Group III used a highly-filled injectable resin composite
Group IV used a resin-modified glass ionomer
and Group V used a bioactive ionic resin. All groups received immediate dentin sealing before nanoceramic resin-based CAD/CAM onlay restorations. After the specimens were subjected to thermo-mechanical loading, they underwent fracture resistance testing and failure mode analysis. RESULTS: No statistically significant difference in fracture resistance was observed among the tested groups. Regarding the mode of failure, irreparable failure was significantly dominant, with no significant difference among the groups. CONCLUSION: Employing injectable restorative materials for cervical margin relocation had no detrimental effect on the fracture resistance of molars receiving nanoceramic resin-based CAD/CAM onlay restorations. CLINICAL SIGNIFICANCE: CAD/CAM onlay restorations preceded by cervical margin relocation using injectable restorative materials could tolerate compressive loading comparably to those without cervical margin relocation.