Using a two-step procedure, radiopaque and biocompatible coatings were obtained, consisting of a tantalum layer deposited by sputtering technique and of an upper organic-inorganic hybrid layer synthesized via sol-gel. As shown by radiographic images, tantalum confers to plastic substrates good X-ray visibility, adjustable via control of deposition time, but its adhesion to the substrate is poor and manipulation easily damages the metal layer. Polymer-titania hybrid coatings, synthesized using poly-ε-caprolactone (PCL) or carboxy-terminated polydimethylsiloxane (PDMS) as organic precursors, were applied on the metal layer as biocompatible protective coatings. Biocompatibility is demonstrated by cytotoxicity tests conducted using vascular wall resident-mesenchymal stem cells (VW-MSCs). Both coatings show very good adhesion to the substrate, showing no sign of detachment upon large substrate deformations. Under such conditions, SEM observations show that the PCL-containing hybrid forms cracks, whereas the PDMS-based hybrid does not crack, suggesting possible applications of the latter material as a protective layer of sputtered tantalum radiopaque markers for flexible medical devices.