The surfaces of indwelling catheters offer sites for the adherence of bacteria to form biofilms, leading to various infections. Therefore, the development of antibacterial materials for catheters is imperative. In this study, combining the strong antibacterial effect of a quaternary ammonium salt (QAS) and the high biocompatibility of tannic acid (TA), we prepared a quaternary tannic acid (QTA) by grafting a synthesized quaternary ammonium salt, dimethyl dodecyl 6-bromohexyl ammonium bromide, onto TA. To prepare antibacterial catheters, QTA was blended with thermoplastic polyurethane (TPU) via melt extrusion, which is a convenient and easy-to-control process. Characterization of the TPU blends showed that compared with those of the QAS, dissolution rate and biocompatibility of QTA were significantly improved. On the premise that the introduction of QTA had only a slight effect on the original mechanical properties of pristine TPU, the prepared TPU/QTA maintained satisfactory antibacterial activities in vitro, under a flow state, as well as in vivo. The results verified that the TPU/QTA blend with a QTA content of 4% is effective, durable, stable, and non-toxic, and exhibits significant potential as a raw material for catheters.