Introduction: Generex A and Generex B (calcium silicate based), Capasio (calcium-phospho-alumino silicate based) along with Ceramicrete-D (magnesium phosphate based) are being introduced as a new generation of endodontic materials with the potential to facilitate bone healing. The aim of this study was to evaluate the biocompatibility and osteogenic potential of these new materials by using primary osteoblasts. Methods: Primary osteoblasts were prepared from rat calvaria and exposed to mineral trioxide aggregate (MTA), Generex A, Generex B, Capasio, and Ceramicrete-D prepared to standardized size and shape (n = 5). Trypan blue staining was used to evaluate cell viability from 1–6 days. Mineralization potential was evaluated by scanning electron microscopy for the presence of mineralized nodules. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests. Results: Only Generex A and MTA allowed cell growth and proliferation throughout the experiment. There were statistically significant differences between groups throughout the experiment beginning on day 1. The greatest amount of cell growth was consistently observed with Generex A and MTA. There was no difference in mineralized nodule formation between any test materials. Conclusions: Generex A was the only new generation endodontic material that supported primary osteoblast growth; no material besides MTA facilitated nodule formation. (J Endod 2011;37:1166–1170)