Preprosthetic surgery has become a routine procedure to obtain sufficient bone quantity and quality for dental implant installation in patients with an initial inadequate bone volume. Although autologous bone onlay or inlay grafting is still the preferred bone augmentation technique, a broad range of synthetic bone substitutes have been developed, for example, calcium phosphate cement (CPC). The introduction of porosity within CPC can be used to increase CPC degradation and bone ingrowth. Therefore, three different strategies to obtain porous CPCs were evaluated in this preclinical study. Instantaneously porous CPC (CPC-IP) was compared with delayed porous CPC in vitro and in vivo. CPC-IP was obtained by the creation of CO(2) bubbles during setting, whereas delayed porous CPC was obtained after the degradation of incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres. As an additional aspect, delayed porous CPC was created by the incorporation of either hollow or dense degradable PLGA microspheres (CPC-hPLGA and CPC-dPLGA). All CPC compositions showed appropriate clinical handling properties and an interconnected porous structure with a final porosity above 70% (v/v). In vitro degradation studies showed the gradual formation of pores and further CPC-matrix dissolution for CPCs containing PLGA microspheres (dPLGA microspheres > hPLGA microspheres). For in vivo evaluation of the CPCs, an augmentation model was used, allowing a CPC injection into a rigidly immobilized Teflon ring on the rat skull. Histological evaluation after 12 weeks of implantation showed bone formation using all three CPCs. Bone apposition reached volumetric amounts of up to 10% of the augmentation area and a maximum augmentation height of approximately 1 mm. CPC-IP showed significantly more bone formation and resulted in a superior bone apposition height compared with both CPCs containing PLGA microspheres. No differences in biological performance were observed between the CPCs containing hPLGA and those containing dPLGA microspheres. Further research is necessary to enhance the bone appositional speed and amount of CPCs for bone augmentation procedures before them being used in a potential clinical setting.