Hydroxyapatite (HA) whisker reinforced polyetheretherketone (PEEK) composites have been investigated as bioactive materials for load-bearing orthopedic implants with tailored mechanical properties governed by the volume fraction, morphology, and preferred orientation of the HA whisker reinforcements. Therefore, the objective of this study was to establish key structure-property relationships and predictive capabilities for the design of HA whisker reinforced PEEK composites and, more generally, discontinuous short fiber-reinforced composite materials. HA whisker reinforced PEEK composites exhibited anisotropic elastic constants due to a preferred orientation of the HA whiskers induced during compression molding. Experimental measurements for both the preferred orientation of HA whiskers and composite elastic constants were greatest in the flow direction during molding (3-axis, C33 ), followed by the transverse (2-axis, C22 ) and pressing (1-axis, C11 ) directions. Moreover, experimental measurements for the elastic anisotropy and degree of preferred orientation in the same specimen plane were correlated. A micromechanical model accounted for the preferred orientation of HA whiskers using two-dimensional implementations of the measured orientation distribution function (ODF) and was able to more accurately predict the orthotropic elastic constants compared to common, idealized assumptions of randomly oriented or perfectly aligned reinforcements. Model predictions using the 3-2 plane ODF, and the average of the 3-1 and 3-2 plane ODFs, were in close agreement with the corresponding measured elastic constants, exhibiting less than 5% average absolute error. Model predictions for C11 using the 3-1 plane ODF were less accurate, with greater than 10% error. This study demonstrated the ability to accurately predict differences in orthotropic elastic constants due to changes in the reinforcement orientation distribution, which will aid in the design of HA whisker reinforced PEEK composites and, more generally, discontinuous short fiber-reinforced composites.