Aim: The purpose of the study was to compare between EndoSequence BC® and EndoSeal MTA® sealers regarding their antibacterial activity against Enterococcus faecalis. Methods: The “Direct contact test" was the method used to evaluate the antibacterial effect of the 2 tested sealers. Each sealer was dispensed at the bottom of 96-well plates. Three unfilled wells were used as control group. Samples were evaluated under three setting conditions: fresh sealer, one week-old, and one month-old. Aliquots of the bacterial suspension were placed on the tested sealers and in the control wells. After incubation for 1 hour, the liquid portion of the suspension evaporated providing direct exposure between the bacteria and the surface of sealers. BHI broth (245 μl) was added then to each well and the plates were gradually mixed for two minutes; 15 μl of the bacterial suspension was transferred from each well to corresponding wells in other plates. The kinetics of bacterial growth in each plate was followed by densitometric measurement every hour for 3 hours, using a spectrophotometer. Results: Endoseal showed the stronger antimicrobial effect in different setting conditions. Both sealers have extended antibacterial activity up to one month. Conclusion: Endoseal is the most effective in eliminating E. faecalis and may be the most useful sealer for preventing bacterial infection when treating root canals.