Introduction: Capasio is being developed as a new generation of endodontic material with potential use as a root-end filling material. The aim of this study was to compare the ability of Capasio and mineral trioxide aggregate (MTA) to penetrate human dentinal tubules and examine the interaction of Capasio and MTA with a synthetic tissue fluid (STF) and root canal walls in extracted human teeth. Methods: Root-end preparations were filled with Capasio or MTA, allowed to set for 4 weeks in STF, and then sectioned at 1, 2, and 3 mm from resected surface. Depth of penetration was evaluated by using scanning electron microscopy (SEM). Next, Capasio and MTA samples were prepared both in 1-g pellets and in root-end preparations. Samples were placed in STF, allowed to set, and then characterized by using SEM, energy dispersive x-ray analysis (EDXA), and x-ray diffraction (XRD) techniques. Results: Penetration of Capasio into dentinal tubules was observed at all levels. No penetration of MTA into dentinal tubules was observed at any level. Both Capasio and MTA formed apatite crystals in the supernatant, on their exposed surfaces, and in the interfacial layers that were similar in structure and elemental composition when evaluated by using SEM and EDXA. XRD analysis of these crystals corresponds with those reported for hydroxyapatite. Conclusions: When used as a rootend filling material, Capasio is more likely to penetrate dentinal tubules. Both Capasio and MTA promote apatite deposition when exposed to STF. (J Endod 2012;38:1093–1096).