Like all biofluid-contacting medical devices, intranasal splints are highly prone to bacterial adhesion and clot formation. Despite their widespread use and the numerous complications associated with infected splints, limited success has been achieved in advancing their safety and surface biocompatibility, and, to date, no surface-coating strategy has been proposed to simultaneously enhance the antithrombogenicity and bacterial repellency of intranasal splints. Herein, we report an efficient, highly stable lubricant-infused coating for intranasal splints to render their surfaces antithrombogenic and repellent toward bacterial cells. Lubricant-infused intranasal splints were prepared by creating superhydrophobic polysiloxane nanofilament (PSnF) coatings using surface-initiated polymerization of n-propyltrichlorosilane (n-PTCS) and further infiltrating them with a silicone oil lubricant. Compared with commercially available intranasal splints, lubricant-infused, PSnF-coated splints significantly attenuated plasma and blood clot formation and prevented bacterial adhesion and biofilm formation for up to 7 days, the typical duration for which intranasal splints are kept. We further demonstrated that the performance of our engineered biointerface is independent of the underlying substrate and could be used to enhance the hemocompatibility and repellency properties of other medical implants such as medical-grade catheters.