Introduction: The aim of this study was to evaluate the effects of calcium hydroxide (CH) and triple (TAP) and double (DAP) antibiotic pastes on the bond strength of an epoxy resin-based sealer (AH Plus Jet; Dentsply DeTrey, Konstanz, Germany) to the root canal dentin. Methods: Sixty-four single-rooted human mandibular premolars were decoronated and prepared using the rotary system to size 40. The specimens were randomly divided into a control group (without intracanal dressing) and 3 experimental groups that received an intracanal dressing with either CH, DAP, or TAP (n = 16). The intracanal dressing was removed by rinsing with 10 mL 17% EDTA followed by 10 mL 2.5% sodium hypochlorite. The root canals were then obturated with gutta-percha and AH Plus Jet sealer. A push-out test was used to measure the bond strength between the root canal dentin and the sealer. The data were analyzed using 2-way analysis of variance and Tukey post hoc tests to detect the effect of the independent variables (intracanal medicaments and root canal thirds) and their interactions on the push-out bond strength of the root canal filling material to the root dentin (P = .05). Results: The push-out bond strength values were significantly affected by the intracanal medicaments (P < .001) but not by the root canal thirds (P > .05). In the middle and apical third, the bond strength of the TAP group was higher than those of the CH and DAP groups (P < .05). Conclusions: The DAP and CH did not affect the bond strength of the epoxy resin based sealer. Additionally, the TAP improved the bond strength of the epoxy resin-based sealer in the middle and apical thirds.