Background: A successful endodontic therapy aims to remove microorganisms, microbial toxins, and necrotic and important pulp tissue remains from the root canal system. The present study was conducted to assess efficacy of different irrigation devices in removal of calcium hydroxide in teeth with simulated internal resorption cavities. Materials & Methods: 48 single-rooted mandibular premolars were selected. The ProTaper Gold technology was used to prepare and decoronate teeth up to F5. Resorption cavities were created by buccolingually sectioning the samples. Group I, or the negative control, consisted of 8 specimens. Group II, or the positive control, consisted of 8 specimens. The remaining specimens were split up into four groups, and for one minute, PUI, XP-endo, EA, and E1 were used to activate the NaOCl and EDTA. Results: Complete CH paste could not be extracted from simulated internal resorption cavities by any of the evaluated groups. Results from PUI and XP-endo files were better and more efficient than those from any other category. While Endo-Irrigator Plus (EI) demonstrated the least amount of CH elimination, EndoActivator (EA) demonstrated results comparable to XP-endo but significantly different with PUI (P < 0.05). Score 0, 1, 2 and 3 in group I was as 100%, in group II was 100%, in group III was 52%, 34%, 14%, in group IV was 53%, 11%, 26% and 10%, in group V was 26%, 15%, 41% and 18%, and in group VI was 5%, 31%, 44% and 20% respectively. The difference was significant (P< 0.05). Conclusion: No irrigation technique was able to completely eradicate CH in artificial internal resorption voids. In this instance, XP-endo eradicated CH as well as PUI, but more effectively than EA and EI plus, while PUI outperformed all other irrigation technologies.