Purpose: The purpose of this study was to test the hypothesis that the pulp medication ferric sulphate (FS) may remain on primary dentin, affecting its microchemical structure and the bond strength of adhesives to primary dentin. Materials and Methods: The effects of FS and pre-bonding conditioning (37% phosphoric acid [PA] for 15 s or a self-etching primer, with or without the use of 2% chlorhexidine [CHX]) on FS-treated primary dentin were characterized using optical microscopy with Masson's and Perls' stains, variable-pressure SEM/energy-dispersive x-ray spectroscopy (VP-SEM/EDS), Fourier transform infrared spectroscopy (FT-IR), and x-ray diffraction. Ferric sulphate was applied for 30 s or 1 h for microchemical analysis. The adhesive interface and the bond strength were studied by VP-SEM/EDS and the μTBS test (1 mm2 bars, crosshead speed 0.5 mm/min), respectively. The study groups were: etch-and-rinse (E&R, Excite) adhesive (group 1); FS+E&R (group 2); FS+CHX+E&R (group 3); self-etching (SE, Adper Scotchbond) adhesive (group 4); FS+SE (group 5); FS+CHX+SE (group 6). Results: Ferric sulphate application produced demineralization, gypsum formation, and adsorption of Fe on the dentin surface, and it modified the collagen structure of primary dentin. There were no effects of FS on bond strength of the tested etch-and-rinse adhesive system. FS slightly reduced the bond strength between the primary dentin and the SE adhesive, and the values were not restored by CHX (group 4 = 17.58 ± 5.52 MPa > group 5 = 14.26 ± 7.08 MPa = group 6 = 13.96 ± 4.87 MPa). Conclusions: Ferric sulphate alters the microchemical structure of primary dentin and can impair the adhesive strength of some self-etching adhesives. Schlagwörter: ferric sulphate, spectroscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength, microscopy, dentition, primary