Objective: This study investigates the effects of Nd:YAG laser irradiation on apical and coronal seals, when used prior to two root canal filling techniques. Background Data: Limited information exists regarding the effects of morphologic changes to dentin walls following Nd:YAG laser irradiation on the sealing ability of root fillings. Methods: Two hundred forty teeth were analyzed by observing coronal and apical leakage of Indian ink (DL), and 60 were analyzed for through-and-through leakage using the fluid transport model (FTM). The Nd:YAG laser parameters were 1.5 W, 100 mJ, and 15 Hz (four times for 5 s at 20 s intervals). Each group consisted of a lased and a nonlased subgroup: each subgroup had root fills done by either cold lateral condensation (CLC) or hybrid condensation (HC). Leakage was assessed after 48 h, and then at 1, 6, and 12 months. The DL group was divided into four groups of 15 teeth for each evaluation point. Through-and-through leakage (L in microliters= day) was measured for 48 h under a pressure of 1.2 atm using FTM, and recorded as L ¼ 0 (L1), 0 < L 10 (L2), or L > 10 (L3). Results: Apical and coronal dye leakage was observed in all groups. Significant differences ( p < 0.05) in apical leakage were found between HC and HC þ Nd after 1, 6, and 12 months, and between CLC and CLC þ Nd at 6 and 12 months. No significant differences were found between laser-irradiated and non-laserirradiated groups with FTM. Conclusion: Pulsed Nd:YAG laser irradiation following root canal preparation may reduce apical leakage in association with hybrid gutta-percha condensation.