The highly complex process-property-structure relationship poses a major challenge in the optimization of plasma sprayed hydroxyapatite coatings. In addition, contradictions in relation to the ideal coating properties exist; a dense, highly crystalline coating is required for long term coating stability, whereas coatings with lower crystallinity dissolve more rapidly but have an improved osteogenic response in vivo. In this study, response surface methodology (RSM) is utilized to investigate the influences and interaction effects of current, gas flow rate, powder feed rate, spray distance and carrier gas flow rate on the roughness, crystallinity, purity, porosity and thickness of plasma sprayed HA coatings. Roughness related to the particle velocity and particle melting, and was highest at low gas flow rates and, due to the quadratic effect of current, at the central current value. High crystallinity resulted at high current and low spray distance due to the presence of bulk crystalline material and recrystallization of amorphous material. Purity was highest at low carrier gas flow rate and high gas flow rate, where particle temperature was reduced. Porosity was dependent on the degree of particle melting and was highest at low gas flow rate and powder feed rate and at high current and spray distance. Coating thickness was determined by the number of particles and the degree of flattening on impact, and was highest at high current, low gas flow rate, high powder feed rate and low spray distance. From this in-depth analysis, predictive process equations were developed and optimized to produce two distinct coatings; a stable coating and a bioactive coating, designed to form the base and surface layers of a functionally graded coating respectively, to provide enhanced osteogenesis, while maintaining long-term stability. Culture of osteoblast-like cells on the coatings demonstrated an increased osteogenic response on the bioactive coating compared to the other groups. Overall, this study identifies parameter effects and interactions leading to the development of optimized coatings with the potential to enhance the functional life of HA coated implants in vivo. (C) 2017 Elsevier B.V. All rights reserved.