Enterococcus faecalis is a microorganism commonly detected in asymptomatic, persistent endodontic infections. Triple antibiotic paste has stood the test of time as a proven antibiotic combination against E. Faecalis. However, problems with this include staining of teeth and standardization of the preparation. Thus, the search for better alternatives and better preparation techniques is still on. To observe the potential of combinations [(Amoxicillin+ Metronidazole, Amoxicillin Clavulanic Acid + Metronidazole; Amoxicillin and Cloxacillin + Metronidazole)] over Triple Antibiotic Paste. Fifty single rooted teeth free from dental caries were selected for the study. Teeth were cut at equal distance from root apex (13mm from apex) with sterile diamond disk and straight hand piece for standardization of root length. The opening of root canal was enlarged with engine driven pro-taper files. To remove the organic and inorganic debris, canal was cleaned with 17% EDTA followed by 2.5% NaOCl for 5min. Distilled water irrigation was done for 5 min to remove any traces of used chemical and then sterilized in autoclave at 1200c for 15 min. at 15 lbs pressure. Bacteria cultured on blood agar plate and at the same time fresh antibiotic combinations were made and placed in the root canals, then incubated in the incubator, under sterile conditions and observed at 24hrs, 48hr and 72hrs. The largest inhibition zones were observed for the Triple Antibiotic Paste, followed by Amoxicillin and Clavulanic acid + Metronidazole group however, the clearest zones were achieved with Amoxicillin and Clavlunic acid + Metronidazole group and the smallest for Amoxicillin and Metronidazole group. The results suggest that though Triple antibiotic showed the maximum inhibition, Amoxicillin and Clavulanic acid combination along with Metronidazole gave the most reliable results. Further studies using the different combinations and different concentrations along with different methods of increasing the shelf life of such medications can be undertaken.