PEEK is a bioinert material that does not chemically bind to native bone tissue and thus formation of natural bone-like hydroxyapatite (HA) coating layer on PEEK has been an important challenge to improve biocompatibility and to preserve mechanical property of PEEK. Among various coating techniques, cold-spray coating method is suitable to form stable HA coating layer on PEEK while maintaining their chemical properties, because it can be conducted in relatively low-temperature range. Therefore, in this research, we used cold-spray coating method to form a thick layer of HA on the topographically complex PEEK substrates with periodic ridges on the surface and implanted in iliac bone defects of minipigs which is known to be similar with human body system. In addition, PEEK cage for clinical usage was coated with HA and inserted in the lumbar intervertebral disc space of minipig. We observed higher ALP activity, calcium production, and BSP production of human bone marrow mesenchymal stem cells on the HA-coated PEEK implants than the bare PEEK group in in vitro test. In addition, two-dimensional histological analysis and three-dimensional micro CT analysis demonstrated that implantation of complex shape of HA-PEEK hybrid implant in in vivo minipig model resulted sufficient biocompatibility and osseointegration for further clinical applications. Notably, due to the enhanced stability of PEEK cage induced from HA coating layer, osseointegration rate of the small HA blocks loaded inside the PEEK cage was also significantly improved which indicates overall increased fusion rate and adherence of the HA-coated PEEK cage. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 647-657, 2017.