Objective <p>This prospective, randomized, post-market, paired-comparison controlled trial compared the 2-year clinical performance of a new universal adhesive, Scotchbond Universal Plus Adhesive (SBU+), with that of Scotchbond Universal Adhesive (SBU). Both were applied as self-etch (SE) adhesives for composite resin restoration of Class I and Class II preparations.</p> Materials and methods <p>Two posterior teeth in each of 51 subjects were randomized in a 1:1 ratio to a restoration with SBU + or to a restoration with SBU (control) applied with the SE strategy. Class I and/or Class II preparations were restored with Filtek Universal Restorative. Two calibrated and blinded examiners evaluated the restorations at baseline, 6 months, 1 year, and 2 years, using the modified FDI criteria. The Wilcoxon signed-rank test was used to compare the outcomes.</p> Results <p>At the 2-year evaluation, retention was 100% for both the SBU + and SBU groups. Regarding fracture and retention, 36 of the 37 SBU+ restorations (97%) were graded “Clinically Excellent/Very Good,” while 1/37 (3%) was graded “Clinically Satisfactory.” All 38 SBU restorations (100%) were graded “Clinically Excellent/Very Good”. Marginal adaptation was clinically acceptable for all restorations at 2 years, with no statistically significant difference between the two adhesive materials. Furthermore, no recurrent caries lesions were observed at 2 years, and no restorations received a “Clinically Insufficient/Unsatisfactory” or “Clinically Poor” grade for any FDI criteria during any evaluation visit.</p> Conclusions <p>At 2 years, SBU+ exhibited clinical efficacy similar to its predecessor, SBU, in Class I and Class II restorations in adult patients when using the self-etch (SE) technique.</p> Clinical relevance <p>Mildly acidic universal dental adhesives may be used for posterior composite restorations without prior phosphoric acid etching.</p>