Objective To evaluate the effects of thermal and mechanical cycling on the metal-ceramic bond strength of machine-milled Ti2448 alloy and commercial pure titanium (cp Ti).Methods Ceramic-cp Ti (n=30) specimens and ceramic-Ti2448 combinations (n=30) were prepared in accordance with ISO 9693. The specimens from each metal-ceramic combination were randomly divided into three subgroups. In group A or the control group, the specimens were only stored in distilled water for 24 h at 37 °C; in groups B and C, the specimens were subjected to 3 000 cycles of thermal cycling between 5 and 55 °C for a dwell time of 60 s and to mechanical cycling of 20 000 or 40 000 cycles with 50 N load and 4 Hz in distilled water at 37 °C. A crack initiation test was performed using a universal testing machine in accordance with ISO 9693. Failure types at the metal-ceramic interface and the morphological and elemental composition of this interface were analyzed using a scanning electron microscope and an energy dispersive spectrometer. Statistical analysis was performed via two-way ANOVA and Tukey’s adjustment test (α=0.05).Results The bond strength of the ceramic-Ti2448 combination was significantly higher than that of the ceramic-cp Ti combination regardless of fatigue conditions (44.86 MPa±1.75 MPa and 29.21 MPa±2.20 MPa for Ti2448 and cp Ti, respectively; PConclusion The metal-ceramic bond strength of cp Ti and Ti2448 is decreased by thermal and mechanical cycling.