Cuffed venous access catheters have become commonplace for hemodialysis access. The major complications of these catheters are catheter thrombosis, catheter fibrin sheathing and infection. When catheter associated bacteremia occurs treatment with antimicrobial therapy alone has been unsuccessful in providing acceptable cure rates. Failed antimicrobial therapy exposes the patient to the risks of prolonged bacteremia, while the alternative, catheter replacement at a new site can lead to central venous stenosis and compromise future long-term upper extremity access. Catheter guidewire exchange when the tunnel tract is clinically not infected theoretically allows the preservation of future access sites and yields a higher treatment success rate while avoiding temporary non-cuffed access placement. We report a series of 23 cases of hemodialysis patients with tunneled cuffed catheters and bacteremia related to the catheter who were treated with the exchange of a new catheter over a guidewire combined with three weeks of systemic antibiotics. Patients eligible for the study required no evidence of tunnel tract infection and defervescence within 48 hours of antimicrobial therapy. Technique failure was defined as repeat infection from any organism within 90 days of catheter exchange. Four patients (18%) redeveloped bacteremia within 90 days of the exchange. The bacteremias developed at 4, 19, 63 and at 74 days days after the exchange. Guidewire exchange in combination with intravenous antibiotics in cases of catheter related bacteremia has an acceptable rate of treatment success and is a viable treatment option in a carefully selected patient population.