Purpose:The purpose of the present study was to investigate the micro-shear bond strength and failure mode of novel "MDP calcium-fluoride releasing" self-adhesive resin cement (TheraCem) with tooth structure (enamel& dentin) and yttrium stabilized zirconia after thermocycling and comparing the results with universal "non-containing MDP" self-adhesive resin cement (Relay X Unicem as a control) Materials and Methods: Enamel and dentin specimens (20 discs each) were obtained by using diamond saw (IsoMet 4000 linear Precision saw, Buehler, USA) with copious water coolant. Twenty zirconia plates were obtained from IPS e.max ZirCad blocks (Ivoclar Vivadent, Schaan, Liechtenstein) and sintered in an inFire HTC speed high-temperature furnace (Sirona Dental System GmbH, Germany). Micro resin cylinders were created on the bonded surface and filled with the tested cements (n= 10 /substrate) group A (control) using non-containing MDP selfadhesive cement Relay X Unicem (3M ESPE) while group B (tested cement) using MDP calciumfluoride releasing self-Adhesive resin cement TheraCem (BISCO, Schaumburg, Illinois, USA). Cements were left to self-cure for 5 minutes. All the specimens were thermocycled for 5,000 cycles (Thermocycler 1100 SD Mechatronik, GmbH). Micro-shear bond strength was measured using universal testing machine and debonded surfaces were examined for failure mode analysis with all morphological and ultrastructure changes using Scanning Electron Microscope (Quanta 250 Field Emission Gun, Netherlands) attached with EDX Unit (Energy Dispersive X-ray Analyses). The results were statistically analysed.Results: TheraCem (tested cement) had a slightly higher (mean±SD) µ-SBS (Mpa) value than RelyX (control) (18.96±4.36, 12.18±3.13; respectively) (P=0.177). Within enamel, TheraCem (6.46±1.37) had a significantly higher (mean±SD) µ-SBS (Mpa) value than RelyX (3.04±0.99) (P=0.002). Similarly, TheraCem in dentine (10.67±1.27) had a significantly higher (mean±SD) than RelyX (6.46±1.74) (P=0.014). As for zirconia, TheraCem (39.76±1.18) had a significantly higher (mean±SD) µ-SBS (Mpa) than RelyX (27.04±1.92) (P<0.001) (822)