PURPOSE: To prospectively evaluate the efficacy of a low-dose, 3-hour infusion of recombinant tissue plasminogen activator (rt-PA) for the treatment of hemodialysis catheter (HDC)-associated fibrin sheaths. This report expands the authors' experience with this technique over that previously reported. MATERIALS AND METHODS: Fifty-five patients with end-stage renal disease (38 women, 17 men) undergoing catheter-directed hemodialysis treatment were evaluated for 124 episodes of HDC dysfunction. This patient group had a mean age of 57 years and an age range of 23-92 years. Radiographic contrast studies and/or clinical evaluation were consistent with the presence of a fibrin sheath on the arterial and/or venous port in all cases. Each patient underwent a thrombolytic infusion consisting of 2.5 mg rt-PA in 50 mL normal saline at 17 mL/h (3-hour infusion) per port. All infusions were performed in the interventional radiology recovery room on an outpatient basis. Patients were followed prospectively for technical success, complications, catheter patency, and long-term outcome. RESULTS: The technical success rate, defined as return of effortless manual aspiration and infusion capability from both ports followed by at least one successful dialysis session, was 91%. No patient was excluded from rt-PA therapy because of contraindications, and the procedure-related complication rate was zero percent. A Kaplan-Meier survival analysis yielded primary patency rates at 30, 60, 90, and 120 days of 0.55, 0.36, 0.25, and 0.15 (SE <.10), respectively; secondary patency rates at 60, 120, 180, and 240 days were 0.70, 0.46, 0.30, and 0.27 (SE <.10), respectively (P < 001). At the end of the study period, all 52 surviving patients continued to undergo catheter-directed hemodialysis and 34 (65%) were using the same catheter present at the time of entrance into the study. Of the 18 patients (35%) requiring catheter exchange, 16 (89%) did for persistent malfunction after rt-PA therapy, one (5.5%) for infection, and one (5.5%) for a fractured hub. CONCLUSION: Thrombolytic therapy with use of a 2.5-mg rt-PA infusion through each port over a 3-hour period would appear to be a safe method for treating HDC-associated fibrin sheaths. Immediate return of catheter function is achieved in most patients, obviating more invasive techniques. Primary patency rates are relatively short, but catheters that fail can be retreated, resulting in secondary patency rates that are substantial and significantly improved.