The aim of this in vitro study was to compare leakage of Enterococcus faecalis ATCC 29212 through root canals of single-rooted extracted human mandibular premolars filled with either gutta-percha/AH Plus or Resilon/Epiphany using the continuous wave of condensation technique. Test and control teeth were suspended in an experimental bacterial leakage setup for 50 days. Kaplan-Meyer curves showed a tendency of the gutta-percha/AH Plus root fillings to prevent leakage better than Resilon/Epiphany counterparts. This tendency, however, was not statistically significant (log-rank test, p = 0.141). The estimated mean time for turbidity to occur in the broth below the suspended root was 35 days (SD = 5 days) in the gutta-percha/AH Plus and 33 days (SD = 4 days) in the Resilon/Epiphany group. It was concluded that within the limitations of this study, there was no apparent advantage of using Resilon/Epiphany over gutta-percha/AH Plus.