This ex vivo study compared saliva coronal microleakage in root canals filled with Resilon/Epiphany Self-Etch (SE) system after final irrigation with different solutions. A total of 60 extracted single-rooted human teeth were instrumented using Mtwo Ni-Ti rotary instruments and divided into two experimental groups (n = 20 each) and positive and negative control groups (n = 10 each). The canals were irrigated with 1.3% NaOCl during instrumentation. After removing the smear layer with 17% EDTA, the root canals in groups A and B were flushed with distilled water and 2% chlorhexidine (CHX), respectively, after which they were obturated with Resilon/Epiphany SE using lateral compaction technique. After sterilizing the whole system with gamma-rays, saliva leakage was tested using a split-chamber model. Specimens were monitored every 24 h for 60 days. The data collected were then analyzed using the chi-square test and Kaplan-Meier survival analysis. As compared with group A, the specimens in group B tended to be more resistant to saliva leakage; however, the difference was not significant (P > 0.05). In conclusion, our findings suggest that 2% CHX is a good conditioner for root canal dentin before use of Resilon/Epiphany SE.