The purpose of this study was to compare root-end sealing using 4-META/MMA-TBB resin with that using conventional retrograde root filling technique, and thereby determine if 4-META/MMA-TBB resin offers long-term prevention against dye leakage from the root canal of human teeth. Thirty-five teeth had the apical 2.5 mm of the root resected. In the Sealing (SB) group, 4-META/MMA-TBB resin was applied to the resected surface. In the Filling (Am and EBA) groups, a root-end cavity was prepared and retrofilled with high copper amalgam alloy or reinforced zinc oxide-eugenol cement. Root canals were filled with methylene blue dye solution. Then, dye leakage outside the root canal was measured for 50 weeks. The integrated amount of leakage in SB group was significantly lower than those in Am group (p < 0.05) and EBA group (p < 0.05). Therefore, it can be concluded that root-end sealing using 4-META/MMA-TBB resin resulted in better, long-term sealing than conventional retrograde root filling.