Ultrasound (US) guided medical devices placement is a widely used clinical technology, yet many factors affect the visualization of these devices in the human body. In this research, an ultrasound-activated film was developed that can be coated on the surface of medical devices. The film contains 2 μm silica microshells and poly­(methyl 2-cyanoacrylate) (PMCA) adhesive. The air sealed in the hollow space of the microshells acted as the US contrast agent. Ozone and perfluorooctyltriethoxysilane (PFO) were used to treat the surface of the film to enhance the US signals and provide durable antifouling properties for multiple passes through tissue, consistent with the dual oleophobic and hydrophobic nature of PFO. In vitro and in vivo tests showed that hypodermic needles and tumor marking wires coated with US activated film gave strong and persistent color Doppler signals. This technology can significantly improve the visibility of medical devices and the accuracy of US guided medical device placement.