ObjectivesThe aim of this study was to evaluate the 24-month clinical performance of universal adhesives on the restoration success of Class I carious lesions.Materials and methodsFive different universal adhesives (Gluma Bond Universal (GU), Clearfil Universal (CU), Prime&Bond Elect Universal (PU), All bond Universal (AU), and Single Bond Universal (SU)) were used in the self-etch and etch-and-rinse modes in 42 patients. The study was conducted with 10 groups, with 20 restorations in each group. The restorations were evaluated at baseline and during a 24-month recall using World Dental Federation (FDI) and the US Public Health Service (USPHS) criteria. The changes in the parameters were analyzed using the chi-square test.ResultsAt the end of 24months, there was no loss of restoration in any group. According to the USPHS, there was no difference in the baseline and 24-month clinical behavior of the restorations (P?0.05). However, according to the FDI, when adhesives were used in the self-etch mode, three adhesives (GU, SU, PU) showed marginal incompatibility, and one adhesive showed (GU) marginal discoloration between baseline and the 24-month follow-up evaluation (P<0.05). There was no significant difference after 24months between etch-and-rinse and self-etch groups according to the results based on both the USPHS and FDI criteria (P?0.05).ConclusionsThe 24-month clinical performance of the evaluated universal adhesives depends on the adhesive strategy.Clinical relevanceThis study helps clinicians to decide in which mode (etch-and-rinse or self-etch) universal adhesives can be safely used.