Various bone substitutes with improved biocompatibility have been developed. Because these products vary in composition and microstructure, it is difficult to understand each feature and make an appropriate selection. Three recently developed highly porous ceramic bone substitutes were evaluated, including two made of hydroxyapatite with different structures (Apaceram-AX: 85%-porosity with micropores, NEOBONE: 75%-porosity without micropores) and one composed of beta-tricalcium phosphate (OSferion: 75%-porosity with micropores) in a rabbit model. Apaceram-AX showed gradual degradation, while NEOBONE remaining intact. OSferion was almost completely degraded at 24 weeks. Numerous osteoclasts were detected in materials with micropores, whether Apaceram-AX or OSferion, but not in NEOBONE. These differences of biodegradability seemed to be related to the presence of micropores. The compressive strength of OSferion increased for several weeks and decreased at a level of cancellous bone. The strength of NEOBONE gradually increased and remained at the highest level among three. The strength of Apaceram-AX increased two to three times that of cancellous bone. Surprisingly, the strength of all materials declined during the initial 1 week, suggesting that great care should be taken in the early period after implantation. These findings may help surgeons to select an appropriate porous substitute based on understanding of their features.