Objective: The purpose of this study was to compare the efficacy of Erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG), and Erbium-doped yttrium aluminum garnet laser (Er:YAG) lasers with passive ultrasonic irrigation (PUI) and conventional syringe irrigation (CSI) for the removal of calcium hydroxide [Ca(OH)2] paste from standardized canal irregularities. Methods: Forty single-rooted human teeth were split longitudinally, forming halves, and cut a standardized groove in canal walls. After filling each groove with Ca(OH)2 paste, the teeth were reassembled and stored for 1 week. Ca(OH)2 was removed with CSI by using 10 milliliters (mL) of 5% sodium hypochlorite (NaClO) and 10 mL of 17% ethylenediaminetetraacetic acid (EDTA), respectively. The teeth were randomly divided into four groups (n=10). CSI group was irrigated with10 mL of 5% NaClO, 10 mL of 17% EDTA, and 10 mL of distilled water with CSI (control group), respectively. In Er:YAG group, 5% NaClO was activated with Er:YAG laser, and in Er,Cr:YSGG group, Er,Cr:YSGG laser equipped with Radial Firing Tip 2 (RFT 2) was used. In the PUI group, PUI was used with 2.5% NaClO. All groups received irrigation with 10 mL of distilled water as final irrigation. The root halves were examined with a stereomicroscope using a 4-grade scoring system. Results: Residues of Ca(OH)2 in artificial grooves were observed in all groups. In Er,Cr:YSGG group, only three specimens got a score of 1 (less than half of the groove is filled). Er,Cr:YSGG group was found slightly higher yet the difference was found to be not significant with other groups. Conclusions: Although Er,Cr:YSGG laser equipped with RFT 2 tip seems to have a superior effect on removing Ca(OH)2 from the standardized canal irregularities, there was no statistically significant difference between the applications.