Objective: Dental pathologies such as caries are the most prevalent disease worldwide with infectious and social complications. During the process of caries formation, the tooth is degraded and demineralization of enamel and dentine leads to the release of large amounts of inorganic phosphate (Pi) within dental tubuli. As Pi has been shown to induce apoptosis in skeletal cells, including osteoblasts and chondrocytes, we questioned whether high concentrations of Pi could affect odontoblast viability, proliferation and apoptosis. Design: Using the odontoblast-like MO6-G3 cell line as a model, we used cell counting and MTS-based colorimetric assays to measure cell viability and proliferation. Apoptosis was assessed using Hoechst nuclei staining and detection of the early apoptotic markers annexin V and Apo2.7. Results: We show for the first time that a high Pi concentration (7 mM) induced a decrease in odontoblast viability and proliferation together with a large increase in apoptosis. These effects were blunted in calcium-free medium, possibly due to the formation of calciumphosphate crystals in the presence of high Pi concentrations. Conclusion: This study contributes to clarifying the effect of Pi on odontoblast viability and apoptosis, which may improve our understanding of the role of Pi during caries formation.