Thin calcium phosphate (CaP) coatings were deposited on titanium substrates by radio frequency magnetron sputtering of hydroxyapatite target in neon (Ne), argon (Ar), krypton (Kr) and xenon (Xe). The influence of the working gas (Ne, Ar, Kr and Xe) on the wettability and biodegradation in the RPMI 1640 synthetic culture medium of the CaP coatings was investigated. This paper is the first comprehensive study of working gas effect on properties of the CaP coatings. There was an increase in the polar component of surface free energy (SFE) and a decrease in the dispersion component of SFE with an increase in the atomic mass of the working gas. All CaP coatings had a pronounced protective effect, reducing double the number of dead cells in culture compared to the Ti control. The most soluble CaP coatings formed in the atmosphere of Xe stimulated the hAMMSCs division, which led to an increase in the total number of cells (208% of the initial culture). Samples with CaP coatings formed in an inert gas atmosphere increased the gene expression (ALPL, BMP6, BMP2) in vitro . The most biocompatible coatings were those formed in the atmosphere of Xe and Ar.