The aim of this study was to investigate margin integrity of Class V composite restorations in demineralized and sound enamel after bonding with different etch-and-rinse and self-etch adhesive systems. Out of a total of 60 specimens from bovine incisors, 30 specimens were demineralized (21 days, acid buffer, pH 4.95) to create artificial enamel lesions. Circular Class V cavities were prepared in all 60 specimens and treated with either an unfilled etch-and-rinse adhesive (Syntac Classic; Ivoclar Vivadent), a filled etch-and-rinse adhesive (Optibond FL; Kerr), or a self-etch adhesive (iBond Self Etch; Heraeus) (n = 10 per group). The cavities were restored with a nanofilled resin composite and thermocycled (5000×, 5-55 °C). Scanning electron microscopy was used to evaluate margin integrity of the composite restorations, and the percentage of continuous margin was statistically analyzed (α = 0.05). Demineralized enamel led to a significantly lower margin integrity when the self-etch adhesive iBond Self Etch was applied, but did not affect margin integrity when the etch-and-rinse adhesives Optibond FL (filled) or Syntac Classic (unfilled) were used. No significant differences in margin integrity in sound and demineralized enamel were observed between the different adhesives. Demineralized enamel reduces margin integrity of composite restorations when bonded with a self-etch adhesive, but does not affect margin integrity when an etch-and-rinse approach is used.