The aim of this in vitro study was to compare the sealing effectiveness of the Erbium:YAG laser to the sealing effectiveness of an ultrasonic device in the preparation of similar retrograde cavities using different retrograde filling materials. After root-canal instrumentation and filling, apices of 60 single-rooted teeth were resected. Retrograde class I cavities 3 mm deep were prepared using an ultrasonic device (group A) and Er:YAG laser (group B). An ultrasonic unit was used with CT-5 retrotip at the frequency of 32 KHz. Laser beam parameters were a pulse of very short duration (100 micros), energy of 280 mJ, and repetition rate of 10 Hz. Cavities of each group of 10 samples were filled with mineral trioxide aggregate (MTA), Super-EBA, and IRM. Microleakage was measured using a fluid transport model. The results showed that cavities prepared with Er:YAG laser have significantly lower microleakage for all tested materials.