Background: This in vitro study aimed to evaluate the persistence of calcium hydroxide (CH) associated with different vehicles on the artificial cavities after removing with sonic activation or conventional needle irrigation (CNI). Methods: Seventy-two extracted single-rooted teeth were instrumented with ProTaper Universal rotary system up to F4. The roots were split longitudinally, and standardized cavities were prepared. The roots were assigned into 3 groups (n=24), according to vehicles used; distilled water, glycerin, and propylene glycol. In each group, cavities were filled with CH mixed with the respective vehicle. After reassembly, the removal of CH dressing was performed with either sonic activation (EDDY) or CNI (n=12). The remnants of CH were assessed under a microscope at ×40 magnification. A four-grade scoring system was used to evaluate. Kruskal-Wallis and Mann-Whitney U-tests were used to compare the data. Results: There was a significant difference among groups (p=0.000). Complete removal of CH was found in the distilled water and propylene glycol groups when EDDY was used. EDDY was significantly more effective than CNI in the removal of CH mixed with distilled water and propylene glycol p=0.001 and p=0,002, respectively. Whereas no significant difference was found between EDDY and CNI in the glycerin group (p=0.219). The lowest CH remnants were found in the distilled water group when CNI was used. Conclusion: The vehicle associated with CH and irrigation activation is important for its retrieval. EDDY provided the complete removal of CH when mixed with distilled water or propylene glycol.