Indiana University-Purdue University Indianapolis (IUPUI) / Background: Numerous studies have reported the use of hydrofluoric (HF) acid as one of the most effective methods for the achievement of a durable bond between glass-based ceramics and resin cements. Nevertheless, there is little information available regarding the potential deleterious effect on the ceramic mechanical strength. Objectives: (1) to investigate the effect of HF acid etching regimens on the biaxial flexural strength of a low-fusing nanofluorapatite glass-ceramic (IPS e.max ZirPress, Ivoclar Vivadent), (2) to study the ability of an unfilled resin (UR) to restore the initial (i.e., before etching) mechanical strength, and (3) to evaluate the effect of HF acid etching on the ceramic surface morphology before and after UR treatment via scanning electron microscopy (SEM). Methods: One hundred and forty-four disc-shaped (15 ± 1 mm in diameter and 0.8 ± 0.1 mm in thickness) IPS e.max ZirPress specimens were allocated into 12 groups, as follows: G1-control (no etching), G2-30 s, G3-60 s, G4-90 s, G5-120 s, G6- 60 + 60 s. Meanwhile, groups (G7- G12) were treated in the same fashion as G1-G6, but followed by silane and UR applications. Surface morphology evaluation of non-etched and etched IPS e.max ZirPress (G1-G12) was carried out by scanning electron microscopy (SEM). The flexural strength was determined by biaxial testing as described in ISO 6872. Statistics were performed using two-way ANOVA and the Sidak multiple comparisons (α = 0.05). In addition, the Weibull statistics were estimated. Results: A significant effect of etching time (p=0.0290) on biaxial flexural strength was observed. Indeed, G4 led to a significantly (p=0.0392) higher flexural strength than G1. Correspondingly, G10 revealed a considerably higher flexural strength than G7 (p=0.0392). Furthermore, biaxial flexural strength was significantly higher for G7 – G12 than for G1 – G6 (p<0.0001). For G1 – G6, G4 showed the highest Weibull characteristic strength while the lowest Weibull characteristic strength was seen in G6. In G7 – G12, the highest Weibull characteristic strength was presented in G10 whereas G7 had the lowest. Finally, the SEM data revealed that the HF acid etching affected the surface of IPS e.max ZirPress by generating pores and irregularities and more importantly that the UR was able to penetrate into the ceramic microstructure. Conclusion: Within the limitations of this study, HF acid etching time did not show a damaging effect on the biaxial flexural strength of the IPS e.max ZirPress ceramic. Moreover, the ceramic biaxial flexural strength could be enhanced after UR treatment.