When hemodialysis catheters allow only poor or no blood flow, it has become established practice in many centers to instill a thrombolytic agent in an attempt to clear the catheter. The catheter survival advantage gained by repeated use of such treatment is not known. In a prospective study, we analyzed all uses of alteplase in the setting of inadequate catheter blood flow in a cohort of 570 catheters over a 2(1/2)-year period. The time from alteplase instillation to the next episode in which it was required or catheter removal for nonfunction or thrombosis was recorded. Survival analysis was used to estimate the additional catheter survival afforded by each treatment. After censoring for elective catheter removal, the overall catheter half-life was 10.2 months. Catheter malfunction or thrombosis was the most common indication for catheter removal (36.3% of all catheters removed). Alteplase instillation was necessary in 2.77% of dialysis sessions. The median time from the first to second treatment or catheter removal for nonfunction or thrombosis was 27 days (95% confidence interval, 15.7 to 32.3). Additional median survival advantage gained from each subsequent treatment ranged from 10 to 18 days. Treatment of recurrent catheter malfunction with alteplase allows for a median of only five to seven additional dialysis sessions before the treatment must be repeated or the catheter must be exchanged. Although associated with minimal disruption to the dialysis schedule, the ultimate clinical benefit and cost-effectiveness of such treatment is doubtful.