The composition of universal adhesives, as well as the adhesive strategy, may influence bonding effectiveness and durability. This study aimed to evaluate the microtensile bond strength (µTBS) and nanoleakage (NL), immediately and after 6-month aging, and in situ degree of conversion (DC), of two universal adhesives (Scotchbond Universal Adhesive, SBU; Xeno Select, XEN) applied with etch-and-rinse (ER) and self-etch (SE) strategies, in comparison with a two-step SE adhesive (Clearfil SE Bond, CSE). Dentin surfaces of fifty human third molars were randomly assigned to the following adhesives: two universal adhesives, SBU and XEN, applied in ER or SE mode and CSE, used as control. Teeth were sectioned into beams to be tested under µTBS, half of them after 24 h, and the rest after 6 months of water aging. Selected beams from each tooth were used for NL evaluation and in situ DC quantification. SBU and CSE showed significantly higher mean µTBS and lower nanoleakage than XEN, regardless of the evaluation time and adhesion strategy. XEN-SE yielded the lowest degree of conversion. Therefore, adhesive properties of universal adhesives to dentin are material dependent, regardless of the adhesion strategy, exhibiting XEN a significantly worse performance than SBU.