Objective: To compare the effect of the pulpotomy medicaments glutaraldehyde, ferric sulfate, and formocresol on the structure and shear bond strength of a self-etch adhesive to the dentin of primary teeth. Method and Materials: Forty human primary molars were sectioned mesiodistally and divided into four groups: group I (control group), dentin specimens were soaked in distilled water for 48 hours; group II, dentin specimens were soaked in 2% glutaraldehyde; group III, dentin specimens were soaked in formocresol; and group IV, dentin specimens were soaked in 15.5% ferric sulfate. All specimens were rinsed with tap water and dried with air. AdheSE One (a self-etch adhesive) and Valux Plus composite resin were applied to the dentin surfaces. The molecular structure of the adhesive itself and adhesive with composite resin were tested using an FTIR spectrometer. Shear bond strength was tested with a universal testing machine. Failure modes analyses were performed with a scanning electron microscope (SEM). Results: Glutaraldehyde showed little changes in the molecular structure of the adhesive itself and adhesive with composite. However, ferric sulfate and formocresol affected the molecular structure of the adhesive alone and the adhesive with composite. The highest mean value of shear bond strength was for the glutaraldehyde group (11.17 ± 4.87 MPa). Ferric sulfate and formocresol significantly reduced shear bond strength after the application of pulpotomy medicaments (7.45 ± 3.73 and 5.31 ± 3.30 MPa, respectively). SEM analysis revealed that most of the specimens failed in cohesive and mixed modes. Conclusion: This study revealed that formocresol and ferric sulfate adversely affect the shear bond strength and molecular structure of the adhesive system to primary dentin. Keywords: bond strength, ferric sulfate, formocresol, glutaraldehyde, infrared, pulpotomy medicaments