Background: Root canal disinfection is one of the main determinants which aids in the healing of the periapical tissues. The present study was conducted to determine antimicrobial efficacy of different endodontics sealers against E. faecalis. Materials & Methods: The present invitro study was conducted in the department of Endodontics. It comprised of three endodontic sealers such as resin based (AH Plus), calcium hydroxide based (Sealapex), and mineral trioxide aggregate based (MTA Fillapex) based against E. faecalis. The study protocol was approved from institutional ethical committee. The diameter of the growth inhibition zones was measured. Results: The mean bacterial inhibition zone at 24 hours in group I was 9.1, in group II was 14.3 and I group III was 6.5, at 48 hours in group I was 7.3, in group II was 12.4 and I group III was 4.1, at 72 hours in group I was 7.1, in group II was 11.5 and in group III was 0. The difference between groups was significant (P< 0.05). Conclusion: Authors found that maximum bacterial inhibition zone against E. faecalis was obtained with calcium hydroxide-based sealer (Sealapex) followed by resin-based sealer (AH plus) and MTA sealer. Key words: Calcium hydroxide, E. faecalis, MTA