Introduction: The purpose of this study was to evaluate the efficiencies of different irrigation protocols in the removal of triple antibiotic paste (TAP) from root canals. Materials and Methods: A total of 127 extracted human maxillary incisor teeth were prepared. Then, root-end resection of 3 mm was accomplished to simulate immature apex model. The root canals were filled with TAP, after 21 days, randomly divided into nine groups according to irrigation systems and solutions (n = 13). Conventional irrigation (CI) groups - Group 1: Root canal irrigation was performed with CI by Peracetic acid (PAA) solution, Group 2: Root canal irrigation was performed with CI by etidronic acid 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) + sodium hypochlorite (NaOCl) solution, Group 3: Root canal irrigation was performed with CI by ethylenediaminetetraacetic acid (EDTA)/NaOCl solutions. Vibringe system groups - Group 4: Root canal irrigation was performed with Vibringe system by PAA solution, Group 5: Root canal irrigation was performed with Vibringe system by HEBP + NaOCl solution, Group 6: Root canal irrigation was performed with Vibringe system by EDTA/NaOCl solution. EndoVac system groups - Group 7: Root canal irrigation was performed with EndoVac system by PAA solution, Group 8: Root canal irrigation was performed with EndoVac system by HEBP + NaOCl solution, Group 9: Root canal irrigation was performed with EndoVac system by EDTA/NaOCl solution. Control Group: (n = 0). Samples were sectioned vertically, and the amount of remaining medicament was scored for each root half and data were statistically analyzed. Results: Among the irrigation systems, CI groups showed the highest scores at both apical and coronal parts (P < 0.05). In comparisons among the solutions, at the apical part, PAA groups showed the highest scores (P < 0.05). At the coronal part, EDTA + NaOCl groups showed the lowest score values (P < 0.05). Conclusion: The use of irrigation systems improved the removal of TAP from the simulated immature root canals. Also, as an irrigation solution EDTA gives more promising results than PAA and HEBP solutions.