Medical device-associated infections present a leading global healthcare challenge, and effective strategies to prevent infections are urgently required. Herein, we present an innovative anti-adherent hydrogel copolymer as a candidate catheter coating with complementary hydrophobic drug-carrying and eluting capacities. The am- phiphilic block copolymer, Poloxamer 188, was chemically-derivatized with methacryloyl moieties and copo- lymerized with the hydrogel monomer, 2-hydroxyethyl methacrylate. Performance of the synthesized copoly- mers was evaluated in terms of equilibrium swelling, surface water wettability, mechanical integrity, resistance to encrustation and bacterial adherence, and ability to control release of the loaded fluoroquinolone antibiotic, ofloxacin. The developed matrices were able to provide significant protection from fouling, with observed re- ductions of over 90% in both adherence of the common urinary pathogen Escherichia coli and encrusting crys- talline deposits of calcium and magnesium salts relative to the commonly employed hydrogel, poly (hydro- xyethyl methacrylate). Additionally, the release kinetics of a loaded hydrophobic drug could be readily tuned through facile manipulation of polymer composition. This combinatorial approach shows significant promise in the development of suitable systems for prevention of catheter-associated infections.