The purpose of this in vitro study was to compare the root-end sealing of the Resilon/Epiphany system (RES) to Pro Root MTA and Super-EBA using a bacterial leakage system. Fifty-five extracted teeth were instrumented and root-ends were resected and ultrasonically prepared. Test materials were placed in the root-end preparations; Streptococcus salivarius was introduced coronally and the apical 4 mm were immersed in BHI culture medium with phenol red indicator. Bacterial leakage was monitored every 24 h for 4 wk. All positive controls leaked within 24 h; none of the negative controls leaked. Based on chi2 analysis (p < 0.05), RES and MTA leaked significantly less than Super-EBA. There was no statistical difference between RES and MTA. RES may be a viable option as a root-end filling material with good surgical isolation.