The purpose of this study was to evaluate the effect of final irrigation with a new endodontic irrigant, QMix 2in1 (Dentsply Tulsa Dental, Tulsa, OK), on sealer penetration into dentinal tubules using confocal laser scanning microscopy.Thirty recently extracted human maxillary incisors were used in the present study. The teeth were instrumented with sodium hypochlorite (NaOCl) irrigation and then divided into 3 groups according to the final irrigation regimen used: (1) control group, 2.5% NaOCl; (2) EDTA + CHX group, 17% (EDTA) followed by 2% chlorhexidine (CHX); and (3) QMix group, QMix 2in1. All teeth were dried and then obturated with gutta-percha and rhodamine B-labeled AH26 sealer (Dentsply DeTrey, Konstanz, Germany). After setting, the roots were sectioned horizontally 3, 5, and 8 mm from the root apex. Sealer penetration into the dentinal tubules was examined by confocal laser scanning microscopy.In the apical sections of the roots, no significant difference was detected in the percentage of sealer penetration between any of the final irrigation groups (P > .05). Both the EDTA + CHX and QMix groups showed significantly more sealer penetration than the control group in the middle and coronal sections. However, no difference was found between the EDTA + CHX and QMix groups in either of these areas (P > .05) CONCLUSIONS: Use of EDTA + CHX or QMix during final irrigation significantly improved sealer penetration when compared with the control group in the middle and coronal sections of the roots; however, no effect was observed in the apical sections.