The goal of the present work was to investigate the effects of several cement preparation parameters on setting and hardening reaction mechanisms and hydroxyapatite (HA) cement properties. A central composite experimental design (CCD) was conducted by choosing particle size, solid to liquid ratio, pH, seed concentration and buffer concentration as design parameters along with compressive strength and setting time being the responses. Tetracalcium phosphate (TTCP) powders were prepared by heat treatment of calcium and phosphate source mixtures in the 1200-1400°C temperature range followed by quenching to room temperature in a dessicator. The second phase used in the formulations (brushite) was prepared by aqueous chemical methods. A series of HA pastes/cements were prepared by changing the above mentioned design parameters. Cements were characterized by a standardized setting time test, mechanical testing machine, SEM and XRD. HA cements with the desired properties can be formulated by using CCD in which the responses were expressed by a second order polynomial equation of the parameters. Compressive strengths for the majority of HA cements were determined to be in the 100-160 MPa range which is significantly higher than those reported in the literature.