Purpose: To investigate the bonding of a new universal adhesive applied using different etching strategies on sound and caries-affected dentin of primary teeth. Materials and Methods: Flat dentin surfaces from 50 primary molars were randomly assigned to 10 groups according to substrate (sound dentin [SD] vs caries-affected dentin [CAD] pH cycled for 14 days) and bonding approach (Scotchbond Universal Adhesive: self-etching, vs dry or wet-bonding etch-and-rinse strategies; Adper Single Bond Plus [two-step etch-and-rinse adhesive] and Clearfil SE Bond [two-step self-etching system] as controls). After 24 h of water storage, bonded sticks with cross-sectional areas of 0.8 mm2 were tested for microtensile bond strength (μTBS). Two sticks from each tooth were immersed in silver nitrate solution in order to evaluate nanoleakage (NL) with SEM. The μTBS means were analyzed using two-way ANOVA and Tukey's tests. For NL, the Kruskal-Wallis and Mann-Whitney tests were used (α = 0.05). Results: The influence of the etching strategy on the bonding performance of the universal adhesive was substrate dependent. The self-etching approach resulted in lower μTBS values and higher silver nitrate uptake into hybrid layers for Scotchbond Universal Adhesive on SD, while no difference among experimental groups was observed in CAD. Conclusion: It is preferable to use the universal adhesive following either a dry- or wet-bonding etch-and-rinse approach on both sound and caries-affected primary dentin. Keywords: dentin, microtensile, nanoleakage, etch-and-rinse, self-etching, one-step adhesive