A ureteral stent with strong resistance to proteins, bacteria, and multivalent ions is crucial for the safe treatment of urologic diseases. Generally, the proteins, bacteria, and multivalent ions present in urine tend to bind to the stent surface, leading to aggregation, nucleation, and subsequent stent encrustation. Stent encrustation can induce or exacerbate urinary tract infections and obstructions, thereby seriously harming kidney function. Although hydrophilic coatings on ureteral stents can reduce the binding of proteins, bacteria, and multivalent ions, encrustation still occurs. To date, preventing stent encrustation formation remains a significant challenge. Here, we grafted dense trimethylamine oxide (TMAO)-derived zwitterionic polymers onto the stent surface via a branched amplification strategy. These zwitterions can strongly bind water molecules, forming a stable hydration layer that repels proteins, bacteria, and multivalent ions from adhering to the surface of the polyurethane ureteral stent, thus rendering the stent anti-encrustation. The results showed that the TMAO-derived zwitterion-coated stents exhibited a significantly reduced encrustation weight (13.8% of the original polyurethane stent) and demonstrated good safety. This approach offers a promising method for enhancing stent encrustation resistance. STATEMENT OF SIGNIFICANCE: This study successfully developed a TMAO-derived zwitterionic coating on the surface of a polyurethane stent, creating a superhydrophilic surface with a minimal contact angle of 5.2