Etch-and-rinse adhesives can cause vasorelaxation via mechanisms occurring in the endothelium and smooth muscle, including the release of nitric oxide (NO). This effect might promote or aggravate bleeding if such adhesives are placed inadvertently on iatrogenic pulp microexposures. The present study assessed the vasoactive potential of a newer generation self-etch adhesive, Clearfil Protect Bond (CPB), on isolated rat aorta. Cumulative concentrations of the primer, bond, and mixture of CPB elicited concentration-dependent relaxation of phenylephrine-induced active tonus in the rat aorta, demonstrating that the tested self-etch adhesive can lead to vasorelaxation of pulp vessels that is mediated by Ca2+ antagonistic effect. The vasorelaxant effect of CPB or its components was mediated neither via endothelium-dependent NO and prostanoid-dependent mechanisms nor by K+ efflux through K+ channels, Mechanical removal of the endothelium did not significantly alter the relaxation induced by CPB. Assuming these data can be extrapolated to the clinical situation, CPB, either in mixed form or by its components, can lead to vasorelaxation of pulp vessels that is mediated by a Ca2+ antagonistic effect. If CPB is placed inadvertently on pulp microexposures during direct pulp capping, this effect might promote bleeding that might impair healing and, via plasma exatravasation, might compromise resin infiltration and polymerization.