Abstract The microstructure, mechanical behaviour, and biocompatibility (cell culture, morphology, and cell adhesion) of nanostructured Ti 45 Zr 15 Pd 35‐ x Si 5 Nb x with x = 0, 5 (at. %) alloys, synthesized by arc melting and subsequent Cu mould suction casting, in the form of rods with 3 mm in diameter, are investigated. Both Ti‐Zr‐Pd‐Si‐(Nb) materials show a multi‐phase (composite‐like) microstructure. The main phase is cubic β‐Ti phase ( Im 3 m ) but hexagonal α‐Ti ( P63/mmc ), cubic TiPd ( Pm3m ), cubic PdZr ( Fm 3 m ), and hexagonal (Ti, Zr) 5 Si 3 ( P63/mmc ) phases are also present. Nanoindentation experiments show that the Ti 45 Zr 15 Pd 30 Si 5 Nb 5 sample exhibits lower Young's modulus than Ti 45 Zr 15 Pd 35 Si 5 . Conversely, Ti 45 Zr 15 Pd 35 Si 5 is mechanically harder. Actually, both alloys exhibit larger values of hardness when compared with commercial Ti‐40Nb, (H Ti‐Zr‐Pd‐Si ≈ 14 GPa, H Ti‐Zr‐Pd‐Si‐Nb ≈ 10 GPa and H Ti‐40Nb ≈ 2.7 GPa). Concerning the biological behaviour, preliminary results of cell viability performed on several Ti‐Zr‐Pd‐Si‐(Nb) discs indicate that the number of live cells is superior to 94% in both cases. The studied Ti‐Zr‐Pd‐Si‐(Nb) bulk metallic system is thus interesting for biomedical applications because of the outstanding mechanical properties (relatively low Young's modulus combined with large hardness), together with the excellent biocompatibility. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1569–1579, 2015.