||Plasma-sprayed hydroxyapatite (HA) coated Ti-6Al-4V is a promising material for biomedical implants. Successful applications of this implant material rely on fundamental understandings of the microstructure characteristics and mechanical behavior of the HA coating. The objectives of the present work are (1) to characterize the heterogeneous features of the HA coating, (2) to quantify the elastic/plastic behavior of the HA coating, and (3) to systematically examine in vitro mechanical integrity of the HA coating under various loading conditions The microstructure characterization of the as-sprayed HA coating demonstrates that it exhibits two distinctive regions on its cross-section, i.e. a crystalline ribbon-like region surrounded by a relatively smooth amorphous region. The OH and O concentrations are also found to decrease with depth from the surface of the HA coating and reach a minimum at the coating/substrate interfaces. A feasible approach that combines the indentation tests with nonlinear finite element modeling has been developed to estimate the elastic/plastic constitutive relation of HA coatings on Ti-6Al-4V substrates. The results show that the Ramberg-Osgood constitutive equation properly describes the deformation behavior of the HA coating. Experiments revealed that conventional cyclic bending tests cannot effectively evaluate the fatigue resistance of the HA coating on Ti-6Al-4V in both air and simulated body fluid (SBF). Alternative approaches including Hertzian indentation and a new shear test method were employed. The fatigue tests of the coating under cyclic Hertzian indentation revealed that the fatigue damage of the HA coating is more severe in SBF than in air, and thin HA coating exhibits less fatigue damage than thick HA coating. The new shear test method was developed to test coatings on metal substrates. This method generates almost the same shear loading on coatings as that in conventional tests and possesses such advantages as simplicity, ease of alignment and use, and the ability to test coatings with different thicknesses. Using the new shear test method, the nominal interfacial shear strength has been evaluated. The coating resistance to cyclic shear loading has been also characterized by the shear stress amplitude versus cycle to failure for the coating samples that failed within l07 cycles as well as by the residual nominal interfacial shear strength for the coating samples that survived l07 cycles. A fatigue failure mechanism of interfacial micro-flaw coalescence was suggested based on the fact that the interface between the coating and substrate does not fully bond.