This study aimed to evaluate the bond strength of a universal adhesive system to enamel surrounding real-life carious cavities. Twenty-eight permanent molars (n = 7) with carious lesions in dentin were subjected to selective carious tissue removal to firm dentin and had their crowns sectioned longitudinally. A universal adhesive system (Single Bond Universal [SBU] used in either etch-and-rinse and self-etch strategies) was compared with an etch-and-rinse Adper Single Bond 2 (ASB) and a self-etch Clearfil SE Bond (CSE) adhesive systems (control systems). Adhesives were applied on the enamel, assumed demineralized, surrounding the cavity margins and on sound enamel (control substrate). Composite cylinders were built (0.72 mm2) and microshear bond strength (µSBS) test was performed after 24 h of water storage. The µSBS values (MPa) were analyzed using two-way ANOVA and Tukey's post hoc tests (α = 0.05). Bond strength values obtained in demineralized enamel surrounding carious cavity margins were significantly lower than that obtained in sound enamel (distant from carious cavity margins) (p = 0.035). The bonding strategy of the SBU did not influenced the bond strength values, which were higher than that obtained with ASB. CSE showed similar µSBS values to ASB and SBU in the self-etch mode. In conclusion, the bond strength to enamel assumed demineralized is lower than to sound enamel. The enamel surrounding carious cavities jeopardize the bonding of universal adhesive system. The bond strength of universal adhesive is similar, regardless to bonding strategy.