A comparative investigation of multicomponent thin films based on the systems Ti-Ca-C-O-(N), Ti-Zr-C-O-(N), Ti-Si-Zr-O-(N) and Ti-Nb-C-(N) is presented. TiC(0.5) + 10%CaO, TiC0.5 + 20%CaO, TiC0.5 + 10%ZrO2, TiC0.5 + 20%ZrO2, Ti5Si3 + 10%ZrO2, TiC0.5 + 10%Nb2C and TiC0.5 + 30%Nb2C composite targets were manufactured by means of self-propagating high-temperature synthesis, followed by DC magnetron sputtering in an atmosphere of argon or in a gaseous mixture of argon and nitrogen. The films were characterized in terms of their structure, chemical composition, surface topography, hardness, elastic modulus, elastic recovery, surface charge, friction coefficient, and wear rate. The biocompatibility of the films was evaluated by both in vitro and in vivo experiments. In vitro studies involved the investigation of the proliferation of Rat-1 fibroblasts and IAR-2 epithelial cells on the tested films, morphometric analysis and actin cytoskeleton staining of the cells cultivated on the films. In vivo studies were fulfilled by subcutaneous implantation of Teflon plates coated with the tested films in mice and analysis of the population of cells on the surfaces. The films deposited under optimal conditions showed high hardness in the range of 30-37 GPa, significant reduced Young's modulus, low friction coefficient down to 0.1-0.2 and low wear rate in comparison with conventional magnetron-sputtered TiC and TiN films. The surface of all films was negatively charged with an outstanding shift between the Ar and Ar + N2 Zeta potential curves that reaches 5 mV at the highest pH values. We did not detect statistically significant differences in the attachment, spreading and cell shape of cultured IAR-2 and Rat-1 cells on the Ti-Ca-C-O-(N), Ti-Zr-C-O-(N) (TiC0.5 + 10%ZrO2 target), Ti-Si-Zr-O-(N) films and the uncoated substrata. The adhesion and proliferation of cultured cells in vitro was perfect at all investigated films. Assessment of the population of cells covering on the Teflon plates coated with the Ti-Ca-C-O-(N) and Ti-Zr-C-O-(N) films after 16 weeks of subcutaneous implantation revealed the high biocompatibility level of tested films and absence of inflammatory reactions in mice. Contrary, the epitheliocytes and fibroblasts cultivated on the Ti-Zr-C-O-(N) (TiC0.5 + 20%ZrO2 target) and Ti-Nb-C-(N) films had disturbing actin cytoskeleton.