© 2022 Istanbul University Press.Purpose The study aimed to compare four irrigation methods for triple antibiotic paste (TAP) removal using micro-computed tomography (micro-CT) analysis. Materials and Methods Forty bovine central incisor teeth were selected, and the root canals were prepared up to #6 Peeso reamer drills. Equal portions of metronidazole, ciprofloxacin, and minocycline were used for the TAP preparation. The TAP was prepared by mixing the powder with distilled water (with a powder to liquid ratio of 1 mg/1 mL). The TAP was introduced to the canals with a lentulo spiral; then, the access cavities were temporarily sealed. After 21 days of storage, the teeth were randomly divided into four equal groups according to irrigation techniques: open-ended, side-vented, double side-vented needle irrigations and EndoActivator irrigation device. The TAP was removed using 17% EDTA (20 mL) and distilled water (5 mL) for all of the groups. The volume of the intracanal medicament before and after the irrigation procedure was recorded by scanning the samples with micro-CT, and the TAP percentage was calculated. The percentages obtained from each group were compared using ANOVA. The significance level was set at p<0.05. Results The results showed that there was no statistically significant difference among the TAP percentage volumes removed by the different irrigation techniques. Conclusion The irrigation techniques used in this study showed similar TAP removal efficiency, however, they could not completely remove the TAP from the root canal systems.