Purpose: To evaluate the bonding performance of a universal adhesive to sound and artificially-created caries-affected dentin, using either the etch-and-rinse or self-etch strategy. Materials and Methods: Flat midcoronal dentin surfaces from 48 third molars were randomly assigned to eight groups according to the substrate (sound dentin and artificially-created caries-affected dentin [pH cycling for 14 days]) and the adhesive or application mode (Scotchbond Universal: self-etch or etch-and-rinse strategies; Adper Single Bond 2 and Clearfil SE Bond, a two-step etch-and-rinse adhesive and a two-step self-etch adhesive as controls, respectively). Then, composite blocks were constructed, the specimens were further stored in water for 24 h, and composite-dentin sticks were prepared (0.8 mm2) and tested under tension at 1.0 mm/min. Data were analyzed with two-way ANOVA and Tukey's test (α = 0.05). Results: All adhesives tested on artificially-created caries-affected dentin presented similar μTBS (p > 0.05), and inferior bonding performance when compared to sound dentin (p = 0.000). On sound dentin, Scotchbond Universal presented higher bond strengths when applied in the etch-and-rinse than self-etch mode, but comparable bond strength in each application mode in relation to the respective control adhesive (p = 0.04). Conclusion: Scotchbond Universal can be used in different application modes when bonded to artificially-created caries-affected dentin; however, the etch-and-rinse strategy improves its bonding ability to sound dentin. Moreover, Adper Single Bond 2 and Clearfil SE Bond presented similar bond strengths, regardless of the dentin condition and comparable performance in relation to each strategy of Scotchbond Universal. Keywords: dentin, pH cycling, caries-affected dentin, microtensile, universal adhesives