The aim of this study is to compare the sealing efficacy of the retrograde cavity preparations prepared and filled with different equipment and materials. In the study, low speed burs, ultrasonic or Er, Cr:YSGG laser devices were used for cavity preparations and ProRoot MTA and MTA-Angelus as filling materials. Seventy-eight single-rooted teeth were instrumented, root filled, and grouped. Root-end cavities were prepared and filled by using the following: Group 1: Low-speed carbide bur + ProRoot MTA; Group 2: Low-speed bur + MTA-Angelus; Group 3: Ultrasonic retrotips + ProRoot MTA; Group 4: Ultrasonic retrotips + MTA-Angelus; Group 5: Er, Cr:YSGG laser tips + ProRoot MTA; Group 6: Er, Cr:YSGG laser tips + MTA-Angelus. Microleakage was measured using a fluid filtration technique. Differences in the fluid movement among groups were analyzed with a two-way analysis of variance (ANOVA) and LSD test. The results showed a significant difference between the groups prepared with laser and carbide bur (p < 0.05). No difference was found between root-end filling materials (p > 0.05). According to the results of the study, the cavities prepared with Er, Cr:YSGG laser demonstrated significantly lower microleakage in all the filling materials considered.