This article reviews the efficacy and safety of warfarin to prevent tunneled cuffed catheter (TCC) thrombosis in the hemodialysis population. Literature searches of PubMed, EMBASE, the Cochrane Library and Google Scholar were performed until April 1, 2007. Bibliographies of relevant articles were reviewed for additional publications. Minidose (1 mg/day) warfarin is ineffective in preventing TCC malfunction. Warfarin titrated to an international normalized ratio (INR) of 1.5–2.0, 1.8–2.5, and 2.0-3.0 was found to decrease the rate of thrombosis in selected patients. Early initiation of warfarin after catheter placement may be advantageous. Despite evidence of efficacy, safety is of greater concern. There were no major bleeds reported at an INR range of 1.5–2.5 specifically in catheter studies. However, an increase in major bleeding episodes has been reported with INR ranging from 1.4 to 3.0 in patients receiving warfarin for other indications (e.g., graft patency or cardiovascular indications). There is insufficient evidence to recommend the routine use of warfarin to prevent TCC thrombosis in all patients, primarily because of safety concerns. There is an increased risk of bleeding associated with warfarin use in the hemodialysis population. If a decision is made to use warfarin on a case-by-case basis, literature to date suggests that an INR target of 1.5–2.5 should suffice. Bleeding must be monitored carefully in this population, especially in patients using antiplatelet medications for concurrent conditions.