Hydroxyapatite (HA) microspheres were successfully synthesized under hydrothermal conditions in the presence of ethylene diamine tetraacetic acid disodium salt (Na(2)EDTA). The morphology and structure of the as-synthesized microspheres were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, and scanning electron microscopy analyses. The morphology of HA was significantly affected by pH, Na(2)EDTA/Ca ratio, and reaction temperature. High pH values could promote the formation of microspheres. The structures were transformed from tight to estrange with decreasing pH. The Na(2)EDTA/Ca ratio affected self-assembled, the ratio of Na(2)EDTA/Ca at 2:2 resulted in the formation of a dense spherical structure. The reaction temperature affected the degree of the density of the microspheres. HA microspheres with high crystallinity can be produced under conditions with high pH, high temperature, and moderate holding time. The mechanism underlying the formation of HA microspheres in the presence of Na(2)EDTA at high pH was proposed. At the initial stage of the reaction, crystals were formed and the trunk appeared with a rod-like HA self-assembly. With prolonged reaction time, dumbbell-like HA was formed. Further growth could produce HA microspheres. (C) 2015 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.