The conditioning of the root canal wall during chemo-mechanical root canal treatment differentially affects the adhesion of root canal sealers. This investigation evaluated the impact of sodium hypochlorite (NaOCl) concentration as used in a root canal irrigation concept called continuous chelation, with 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) contained in the NaOCl solution that is applied. Fourier-transform infrared spectra of the dentinal wall were gathered. The consequential effects on push-out bond strength of an epoxy resin (AH Plus) versus a hydraulic CaSi sealer (BioRoot RCS) were assessed. Single-rooted extracted human teeth were used and irrigated with pure NaOCl at a concentration of 0% (physiological saline), 2.5%, or 5.25%. Dual Rinse HEDP (9%) was added to the solutions, or not added for further control. Pure NaOCl solutions caused a decrease in the amide III: phosphate ratios, which was counter-acted by the addition of HEDP. It was observed that the adhesion of the epoxy resin sealer under investigation was negatively affected by this NaOCl deproteinization of the canal wall in a dose-dependent manner, while the opposite was observed with the CaSi sealer. HEDP when used in conjunction with NaOCl was beneficial for the adhesion of both sealers.