Bismuth and strontium ions were successfully substituted into hydroxyapatite (HAP) lattice upon the chemical formula BixSryCa10 x yoPO4thorn 6oOHthorn 2 via coprecipitation microwave-assisted route. The samples with different concentrations were investigated via X-ray diffraction, Fourier transform infrared, field emission scanning electron microscopy, thermogravimetric analysis and microhardness. In addition, lattice parameters, lattice distortion and crystallite size upon different models were computed. The two ions competed to replace both Ca 2? sites, and it was found that Bi 3? preferred Ca(2), while Sr 2? selected Ca(1). The hardness was enhanced via substitution where the highest value reached 3.1 GPa at the highest concentration of Bi 3? ions. This study has displayed that co-substituted ions into HAP can cause a great influence on its physico-chemical properties. The thorough study of the co-substitution effects is needed to deepen the understanding of synthetic HAP which may contribute in growth its applications particularly in bone tissue engineering.