Background: Endodontic root canal sealers provide antimicrobial activity and help to resolve periapical lesion. The aim of the present study was to evaluate the antimicrobial efficacy of different root canal sealers against enterococuus faecalis. Method: Five root canal sealers were selected Zinc Oxide Eugenol, Endoflas FS, Endomethasone, AH plus, Apexit and ampicillin as control group. The present study is carried out following the method described by Kriby, Bauer (1966). Entercoccus faecalis organisms zone of inhibition was measured at 24 and 48 hours with the help of vernier caliper. ANOVA and Whitney U test were used to compare the data. Results: It was found that the mean value in Ampicillin (control) (7.80+0.42) is significantly higher than the mean values in the entire study group (P<0.05). and the mean value in Endomethasone (2.40+0.52) in significantly higher than the mean value in Zinc Oxide Eugenol (1.5+0.53), Endoflas (1.40+0.52), AH –plus (0.000+0.000) and Apexit (0.46+0.24) (P<0.05). Conclusion: Endomethasone showed significantly greater antimicrobial effect against E. faecalis. Apexit was less effective against E .feacalis Key words: Irrigation, Enterococuus faecalis