ABSTRACT Background: The major factor for endodontic failure is the inability to control and prevent persistent microbial infections. Irrigants and untracanla medicaments are used to reduce microorganisms. A good combination has to be studied Aim: To compare the antibacterial efficacy of 3 irrigants- 3% Sodium Hypochlorite, 3% Calcium Hypochlorite and 2% Chlorhexidine against E.faecalis biofilm and then to assess if any further reduction in microbial load after the placement of 2 intracanal medicaments - Calcium hydroxide and 1% Metronidazole + 0.25% Chlorhexidine. Materials and Methods: Sixty- three mandibular incisors were used to form a 6-week E. faecalis dentinal biofilm. Canals were instrumented up to Protaper F2. The tooth samples were divided into 4 groups as per irrigation regimen as Group A- Sodium Hypochlorite (n=20), Group B- Calcium Hypochlorite (n=20), Group C- Chlorhexidine (n= 20) and Group Control (n =3). The Groups A, B and C were further divided into 2 subgroups each for the placement of intracanal medicament. After 7 days, the specimens were analysed for presence of colonies of E.faecalis. Results: When compared to control group, significant difference was observed between all test groups. But statistically no significant difference was found between the three irrigants. Both Calcium hydroxide and Metronidazole +Chlorhexidine have effectively destroyed the remaining E.faecalis culture, hence exhibiting their bacteriocidal nature without any significant difference between them. Conclusion: Irrigation alone did not eliminate E.faecalis, combining Irrigant with medicament eliminated all E.faecalis and different combinations of irrigants and medicaments were equally effective.