In the current trend of materials used for dentin hypersensitivity treatment, calcium–phosphate-containing desensitizers are expected to have advantages in oral environment. A newly formulated desensitizer containing tetracalcium phosphate and dicalcium phosphate anhydrous (CPD-100) was evaluated in comparison to oxalate containing desensitizer (SS) regarding permeability reduction (PR%) by measuring hydraulic conductance on the etched dentin discs in vitro. CPD-100 exhibited mean PR% of 91%, which significantly increased to 98% after immersion in artificial saliva (AS) for 4 weeks (p < 0.001), while SS showed a significant decrease from 99% to 93% (p < 0.01). SEM observation showed newly formed crystallites on CPD-100 treated dentin, which did not exist in SS treated dentin after AS immersion, suggesting that calcium oxalate inhibited formation of new calcium–phosphate minerals. Five-minute acid challenge did not significantly affect PR% of dentin treated by any of the desensitizers. The energy dispersive X-ray spectroscopy (EDS) analysis indicated that the formed layer of CPD-100 were minerals with similar Ca/P ratio to hydroxyapatite. In conclusion, the newly developed calcium–phosphate desensitizer has the potential to exhibit long-term stability in the oral environment, owing to its chemical properties that promote the crystal growth in salivary fluid. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.