Aim: To determine antibacterial efficacy of three antibacterial agents and combination against endopathogens. Methodology: Bacterial strains associated refractory endodontic conditions were used to determine MIC of Clindamycin (C), Metronidazole (M), Doxycycline (D) and combination CMD, against Candida albicans, Pseudomonas Aeruginosa, Escherichia Coli, Enterococcus Faecalis, Streptococcus Mutans, Bacillus subtilis subspe spizizenii, Actinomyces Actinomycetemcomitans. The data was analyzed using paired ‘t’ test, one way ANOVA and Tucky’s post Hoc HSD. Results: Clindamycin (C) inhibited C. albicans (90%) and S. mutans (90%) while P. Aeruginosa, E. Coli, E. Faecalis, B. subtilis and A. actinomycetemcomitans were resistant to it. Metronidazole (M) did not inhibit any of the bacteria. Doxycycline (D) inhibited C. albicans (90%), P. Aeruginosa (90%), and S. mutans (90%), while E. Coli, E. Faecalis, B. subtilis and A. actinomycetemcomitans were resistant. The combination CMD inhibited all the bacteria significantly. Conclusion: Combination CMD can be used against resistant endopathogens for predictable results.