ObjectiveThe purpose of the study was to evaluate the effect of hydroxyapatite (HA)-based desensiti-zing agents and determine their influence on the bonding performance of mild universal adhesives.MethodsMid-coronal dentin samples were sectioned from human third molars and prepared for a dentin-sensitive model. According to desensitizing applications, they were randomly divided into four groups for the following treatments: no desensitizing treatment (control), Biorepair toothpaste (HA-based desensitizing toothpaste) treatment, Dontodent toothpaste (HA-based desensitizing toothpaste) treatment, and HA paste treatment. Dentin tubular occlusion and occluded area ratios were evaluated by scanning electron microscopy (SEM). Furthermore, All-Bond Universal, Single Bond Universal, and Clearfil Universal Bond were applied to the desensitized dentin in self-etch mode. The wettability and surface free energy (SFE) of desensitized dentin were evaluated by contact angle measurements. Bonded specimens were sectioned into beams and tested for micro-tensile bond strength to analyze the effect of desensitizing treatment on the bond strength to dentin of universal adhesives.ResultsSEM revealed that the dentin tubule was occluded by HA-based desensitizing agents, and the area ratios for the occluded dentin tubules were in the following order: HA group>Biorepair group>Dontodent group (P<0 .05). contact angle analysis demonstrated that ha-based desensitizing agents had no statistically significant influence on the wettability of the universal adhesives (P>0.05). The SFE of dentin significantly increased after treatment by HA-based desensitizing agents (P<0 .05). the micro-tensile bond strength test showed that ha-based desensitizing toothpastes always decreased the μtbs values (P<0 .05), whereas the ha paste group presented similar bond strength to the control group (P>0.05), irrespective of universal adhesive types.ConclusionHA-based desensitizing agents can occlude the exposed dentinal tubules on sensitive dentin. When mild and ultra-mild universal adhesives were used for subsequent resin restoration, the bond strength was reduced by HA-based desensitizing toothpastes, whereas the pure HA paste had no adverse effect on bond strength.