Dicalcium phosphate dihydrate (DCPD) cements are attractive biomaterials for bone repair, and a number of different DCPD cement formulations have been proposed in the literature. In this study, we have specifically compared monocalcium phosphate monohydrate (MCPM)/hydroxyapatite (HA) and MCPM/β-tricalcium phosphate (β-TCP) formulations to test the hypothesis that DCPD cement chemistry affects the degradation properties and cytocompatibility of the cement. Using simple in vitro models we found that MCPM/β-TCP formulations degraded primarily by DCPD dissolution, which was associated with a slight pH drop and relatively low mass loss. Cytocompatibility testing of cement conditioned culture media revealed no significant change in cell viability relative to the negative control for all of the MCPM/β-TCP formulations. In contrast, the MCPM/HA formulations were prone to undergo rapid conversion of DCPD to HA, resulting in a sharp pH drop and extensive mass loss. A stoichiometric excess of HA in the cement was found to accelerate the conversion process, and significant cytotoxicity was observed for the MCPM/HA formulations containing excess HA. Collectively, these results show that, although the product of the setting reaction is the same, DCPD cements produced with MCPM/HA and MCPM/β-TCP formulations differ significantly in their degradation properties and cytocompatibility. These differences may have important implications for the selection of a DCPD cement formulation for clinical application.