Abstract: Antibacterial coatings have been considered as an effective method for preventing the implant-associated infections caused by the bacterial colonization. In this study, we report a water-insoluble polyelectrolyte–surfactant complex, poly(hexamethylene biguanide) hydrochloride–sodium stearate (PHMB–SS) that can be facilely coated onto the surfaces of biomedical catheter and kill the bacteria by releasing the PHMB and prevent the generation of the biofilm. The PHMB–SS-coated surfaces showed better bactericidal activity toward Staphylococcus aureus and Escherichia coli. The PHMB–SS-coated catheters could not only relatively prevent the bacterial colonization in vitro but also in an implant-associated bacterial infection animal model in vivo. Moreover, no significant cytotoxicity and host response were observed in vitro and in vivo, indicating the high biocompatibility of the coating. The water-insoluble antibacterial coating reported in this work represents a novel approach to build a simple and effective coating for the prevention of device-associated infections.