We investigated the influence of different endodontic irrigants on the push-out bond strength of the obturation materials RealSeal SE and AH Plus. In our study, 200 human root canals were prepared and divided into two groups according to the filling material. Each group was divided into five subgroups according to the irrigation protocol [0.9% saline (control), 3% NaOCl, 3% NaOCl with saline, 17% EDTA, and 2% CHX]. After obturation, roots were sliced into 1-mm discs for push-out assessment. Two-way analysis of variance and the Kruskal–Wallis test were performed for pair-wise comparisons. AH Plus exhibited a significantly higher bond strength than RealSeal SE, except with saline alone. Within the AH Plus groups, no significant differences existed between the irrigants. The bond strength of RealSeal SE with saline alone or with NaOCl and saline did not differ from that of AH Plus with saline alone. However, the push-out bond strength of RealSeal SE decreased by approximately half (compared with RealSeal SE with saline alone) after rinsing with NaOCl alone, EDTA, or CHX. Conclusion: The bond strength of RealSeal SE is highly influenced by the irrigant used.