Purpose: To evaluate the effect of different application modes of a recently introduced self-etching ceramic primer on the microshear bond strength (μSBS) and ceramic surface-etching pattern of two glass-ceramic surfaces. Materials and Methods: Twenty-two CAD/CAM blocks of lithium disilicate (LD) and feldspathic glass ceramic (VTR) were each cut into 4 rectangular sections (n = 88 for ceramic surface). The LD and VTR specimens were divided into one control group (hydrofluoric acid + silane coupling agent [HF+SII]), and 10 experimental groups using Monobond Etch and Prime (MEP) applied for a combination of scrubbing times (5, 10, 20, 40, and 60 s) and reaction times (20 or 40 s). After each treatment, Tygon matrices (n = 8) were filled with a resin cement and light cured for each ceramic specimen. The specimens were stored in water at 37°C for 24 h and subjected to the μSBS test. The failure pattern and μSBS were statistically evaluated (α = 0.05). In addition, the ceramic surface etching pattern was analyzed using scanning electron microscopy. Results: For the LD groups, the application of MEP 60/40 resulted in a higher mean μSBS compared to HF+SI (p 0.05). Groups 5/40, 10/40, and 20/40 resulted in mean μSBS similar to that obtained by HF+SI (p > 0.05). For VTR, no significant difference was observed among the groups (p = 0.32). Compared with MEP, HF better promoted the dissolution of glass matrix for both ceramics. However, prolonged MEP scrubbing or reaction caused significant dissolution of the glass matrix for both evaluated ceramics. Conclusion: Active and prolonged application of MEP may be a viable alternative to HF+SI for increasing the bond strength to LD. Keywords: hydrofluoric acid, lithium disilicate, scanning electron microscopy, self-etching ceramic primer