In occluded hemodialysis catheters, thrombolytic agents are used to dissolve fibrin clots, reestablish blood flow and allow the patient to continue with hemodialysis treatment. Prior to 2001, urokinase was the indicated fibrinolytic for hemodialysis catheter thrombolysis. However, when urokinase became unavailable in the United States, New Hanover Regional Medical Center developed and implemented a protocol for the use of another fibrinolytic, reteplase, to lyse catheter occlusions. The purpose of this retrospective analysis was to assess the safety and efficacy of reteplase in opening occluded catheters in a series of patients receiving hemodialysis. Between January 1 and June 30, 2002, 59 patients could not complete dialysis, because of either poor arterial blood flow or elevated venous resistance. Reteplase, 0.4 U, was administered to the lumen of occluded catheters. After 30 min dwell times, the lumens were aspirated. If flow could not be sufficiently reestablished, a second reteplase dose was administered. Efficacy endpoints were defined as the ability to complete hemodialysis and achieve flow rates of ≧250 ml/min. Safety endpoints were defined as the occurrence of allergic reactions or bleeding. Eighty-five percent (50/59) of the patients were able to complete their hemodialysis session following reteplase administration, with 70% (41/59) able to sustain blood flow rates of ≧250 ml/min. Of the 50 patients who successfully completed dialysis, 66% (33/50) required only one 0.4-unit dose of reteplase per lumen while 34% (17/50) required a second dose. No instances of bleeding or allergic reactions were noted.