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Background: Considering the irregular shape of the root canal, removing inflamed pulp and granulation tissue completely from internal resorption cavities during chemomechanical preparation can be challenging. This study aimed to evaluate the effectiveness of passive ultrasonic irrigation (PUI) compared to mechanical activation with Easy Clean in the removal of organic tissue from simulated areas of internal root resorption., Methods: The root canals of 72 extracted single-rooted teeth with oval canals were instrumented with Reciproc R25 instruments. After root canal preparations, the specimens were split longitudinally, and semicircular cavities were prepared using a round bur on each half of the roots. Samples obtained from bovine muscle tissue were weighed and adapted into semicircular cavities. The roots were reassembled and joined, and the teeth were divided into six groups (n = 12) according to the irrigation protocol: Sodium hypochlorite (NaOCl) without activation; NaOCl + PUI; NaOCl + Easy Clean; distilled water without activation; distilled water + PUI; and distilled water + Easy Clean. After irrigation protocols, the teeth were disassembled, and the remaining organic tissue was weighed. Data were analyzed by two-way ANOVA and Tukey's post hoc test (p < 0.05)., Results: None of the experimental protocols totally removed the bovine tissue from simulated cavities. Tissue weight reduction was significantly affected by the activation method (p < 0.05) and by irrigation solution (p < 0.05). Groups with NaOCl irrigation presented higher tissue weight loss when compared to distilled water, for all irrigation methods (p < 0.05). The use of Easy Clean resulted in the greatest tissue weight loss (42.0%-Distilled water/45.5%- NaOCl) compared to those of PUI (33.3%-Distilled water/37.7%- NaOCl) and no activation (33.4%-Distilled water/38.8%- NaOCl) (p < 0.05). However, no differences were observed between PUI and no activation groups (p > 0.05)., Conclusions: Mechanical activation with Easy Clean enhanced organic tissue removal from simulated internal resorption more effectively than PUI. Easy Clean for agitation of the irrigating solution is effective in removing simulated organic tissues from artificial internal resorption cavities, being an alternative to the use of PUI., (© 2023. The Author(s).)