Endocrowns represent a conservative and esthetic restorative alternative to full coverage crowns. They can be constructed using various CAD/CAM materials that can provide a modulus of elasticity similar to that of teeth. The ability to use of such materials in composite blocks that can be easily repaired is also an advantage, provided appropriate bonding performance is ensured. This study, therefore, evaluated the marginal gap and fracture resistance of two CAD/CAM endocrown materials using two bonding protocols. Thirty-two mandibular molars were evaluated in two groups based on the material type: a Cerasmart group (GC America Inc; n ¼ 16) acting as the control and a Ceramill COMP group (Amann Girrbach, Germany; n ¼ 16). These groups were then classified according to the bonding protocol used: a total-etch bonding protocol (n ¼ 8) and a self-etch bonding protocol (n ¼ 8) implemented using RelyX ultimate adhesive resin cement (3M ESPE). The samples were then subjected to aging by simulating a 1-year thermomechanical process. The marginal gap results were statistically insignificant across the material and bonding protocol groups before thermo-mechanical aging. Thermo-mechanical aging significantly reduced the marginal gap distance for Ceramill COMP endocrowns cemented using the total-etch protocol (p ¼ 0.002). No statistically significant difference was recorded for the fracture resistance in either the material or bonding protocol groups (p ! 0.05). Both materials and bonding protocols can, therefore, be used in the posterior region providing conservative treatment, adequate marginal gap and fracture resistance.