Hydrophilic lubricant coatings with antifouling properties are commercially applied to urological devices, such as ureteral stents (USs), to inhibit biofilm formation and reduce the likelihood of infectious encrustation. However, their long-term effectiveness is limited due to the lack of active and precise antibacterial activity. Herein, this work reports a hydrophilic lubricant (defined as SA-PU/PVP) coating with smart urease-responsive antibiotic release functionality, achieved by incorporating the antibiotic sulfanilamide-conjugated polyurethane (SA-PU) polymers into a commercial lubricant coating agent containing hydrophilic polyvinylpyrrolidone (PVP). During the initial implantation period, the hydrophilic PVP chains rapidly absorb urine on the coating interface, forming a lubricating layer with the desired antifouling activities that reduce the attachment of host proteins, bacteria, and urate crystals by over 90%. As time progresses and the bacteria proliferates and produces urease, the urease enzymatically degrades the urea linkages in the SA-PU/PVP coating, actively releasing SA antibiotics on demand to prevent biofilm formation and encrustation. Benefiting from this synergistic antifouling and smart antibacterial activities, the SA-PU/PVP-coated US exhibits superior performance in preventing infectious encrustation in a porcine model over a 7-week period, surpassing the effectiveness of a commercial hydrophilic lubricant US. This coating strategy offers a practical solution for inhibiting urological device-associated complications.