Background and purpose: One of the most common complications of catheter in hemodialysis patients is infections and many methods have been proposed to prevent it. This study compared the effects of heparin lock-antibiotics and heparin to prevent infections in patients undergoing hemodialysis.Materials and methods: This single blind clinical trial included 122 patients who were randomly assigned to receive heparin lock (group A) or heparin-antibiotic lock (group B). The subjects in each group were matched for the presence or absence of risk factors. Occurrence of any of the four symptoms of fever, chills (if no other obvious source of infection was found), redness, purulent discharge was considered catheter-site infection. The medication regimens were cefazolin (5 mg/dl) and heparin 2500 IU/ml.Results: The mean age of patients in Group A and B were 57.12±17.34 and 57.61±19.64 years, respectively (P=0.088). The patients who developed infections included 22 (36%) patients in group A and 11 (18%) patients in group B (P=0.02).Conclusion: Heparin-cefazolin lock in group B considerably decreased the incidence of catheter infection. Therefore, it could be used as an effective method to prophylaxis of hemodialysis catheter infection.