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Multi-ion doping in synthetic HA was carried out using high energy planetary ball milling followed by calcination at 1250 °C for 2 h. The influence of Sr +2 , Zn +2 , Ag + , and F - ion doping on crystallinity and crystallite size was analyzed using Taguchi design of experiments (DOE) and optimal concentration of different dopants has been identified to achieve desired crystallinity and crystallite size. The doped HA samples have been characterized using X-ray diffraction and Fourier transform infrared spectroscopy to determine their phase purity, degree of crystallinity, crystallite size and functional groups. Standard Analysis of variance (ANOVA) showed relatively high contribution of Sr +2 and Zn +2 doping in changing the crystallinity and crystal size of HA compared to the effect of Ag + and F - doping. Our analysis demonstrated strong interaction between dopants at binary level doping, while ternary and quaternary doping of elements did not exhibit any interaction in influencing the crystallinity and crystallite size of HA. In general, multi-ion doping in HA found to decrease its crystallinity from 92% to 72% (max.), but enhance the hardness, depending on the type and concentration of doping element. Similarly, a minimum crystallite size of 31 nm was achieved with some binary compositions and other combinations resulted in crystallite sizes up to 59 nm. The compositions that ensure desired crystallinity and crystallite size can also provide high hardness. Our results can be used to tailor the composition of HA in achieving desired functional properties, dependent on crystallinity and crystallite size, such as strength, bioactivity and degradation to suit variety of implant applications.