The traditional irrigation techniques have failed to remove Antibiotic pastes completely from root canal system. So, the role of agitation might be crucial in its removal. Aim: To comparatively evaluate the efficacy of the EndoActivator System (EA), Passive Ultrasonic Irrigation (PUI) and Self Adjusting File (SAF) system on the removal of Double Antibiotic Paste (DAP) from the root canals. Methodology: 60 extracted human single–rooted teeth were selected and root canal preparation was performed using ProTaper Universal rotary instruments till F3. The specimens were then split longitudinally, and 2 standardized grooves were prepared in the coronal and apical part of each segment. DAP was placed in the grooves for 4 weeks, and the root halves were reassembled. EA System, PUI and SAF system were used for the removal of DAP. The root segments were disassembled, and the amount of remaining antibiotic pastes was evaluated under a stereomicroscope using a 4–grade scoring system. The data was evaluated using appropriate statistical analysis. Results: Passive UltraSonic Irrigation shows maximum removal while sonic endoactivator shows the least removal of DAP. Conclusion: The newer irrigation systems can be a viable alternative to the conventional syringe irrigation in removing DAP from the root canal