© 2015 Elsevier B.V. The biocompatibility and osteoconductivity of hydroxyapatite (HA) coatings have led to their use in a wide range of applications in dentistry and orthopaedics. One such application is for the uncemented fixation of implants, where coatings are commonly applied to titanium implants using a plasma thermal spraying process. The spraying process is affected by a large number of parameters leading to highly complex process-property-structure relationships. In a step forward from one-at-a-time analyses, this study used Design of Experiment (DOE) methodology to investigate the simultaneous effects of key plasma spray process parameters on hydroxyapatite coatings for biomedical applications. The effects of five plasma spray process parameters (current, gas flow rate, powder feed rate, spray distance and carrier gas flow rate) on the roughness, crystallinity and purity of hydroxyapatite coatings was determined using a fractional factorial design. The results of this study enabled identification of consistent and competing influences within the process and the identification of some first order interactions. In particular, the diffuse particle size of the HA feedstock powder was found to influence the responses observed within the parameter range investigated. The roughness of HA coatings was found to relate to the particle velocity and the degree of particle melting occurring, with higher coating roughness resulting when current was high, gas flow rate was low and powder feed rate was high. Highest coating crystallinity resulted at high current, low spray distance and low carrier gas flow rate. Under these conditions deposition of larger HA particles resulted leading to higher amounts of bulk crystalline material and the low spray distance increased the substrate temperature allowing amorphous material to recrystallise. Coating purity relates directly to thermal decomposition of the particles within the plasma jet with a high purity coating resulting at low particle temperatures i.e. at the lower ranges of powder feed rate, spray distance and carrier gas flow rate. This study thus brings greater clarity on the effects of plasma spray process parameters on the properties of resultant hydroxyapatite coatings.