This study aimed to compare four final irrigation protocols (passive ultrasonic irrigation [PUI], EndoVac, Self-Adjusting File [SAF] and EasyClean) on the removal of accumulated hard-tissue debris (AHTD) from mesial canals of mandibular molars through microcomputed tomographic (micro-CT) analysis. Forty mesial roots of mandibular molars presenting isthmuses type I or III were scanned in a micro-CT device and instrumented up to Reciproc R40 instrument. After the completion of canal preparations, root canals of each group were submitted to a final rinse using 20mL of solution (16mL of 5.25% NaOCl and 4mL of 17% EDTA) in a total time of 5min according to one of the four final irrigation protocols (n = 10): PUI, EndoVac, SAF and EasyClean operated at reciprocating motion. The sample was scanned again after canal preparation and after the use of the final irrigation protocols, and the registered data sets were examined to evaluate the percentage of AHTD. Data were statistically compared using the Tukey test with a significance level set at 5%. All groups presented a decrease on the accumulation of hard-tissue debris after the use of the final irrigation protocols (P < 0.05). No significant differences in the removal of AHTD were observed among the final irrigation protocols (P > 0.05). All final irrigation protocols showed the same effectiveness in the removal of AHTD. None of them was able to render mesial canals of mandibular molars completely free from packed debris. This study highlighted that all final irrigation protocols (PUI, EndoVac, SAF, and EasyClean) promoted a similar removal of AHTD. However, none of the final irrigation protocols was able to render mesial canals of mandibular molars completely free from packed debris.