A variety of interventional techniques have been developed to restore function to dysfunctional tunneled hemodialysis catheters (THC). The relative efficacies of these techniques were evaluated retrospectively to determine which therapy might be most beneficial. The records of malfunctioning THCs referred to interventional radiology between November 1995 and December 1999 were retrospectively reviewed. Dysfunctional THCs were studied using DSA images obtained while injecting contrast through the lumens of the THCs. The interventions performed were categorized into 1 of 5 groups: no treatment or conservative measures such as vigorous flushing; advancing a guidewire through the THC to reposition the catheter tip or to dislodge a small thrombus; catheter exchange over a guidewire; fibrin stripping of the THC using a loop snare; or prolonged (4 or more hr) direct thrombolytic infusion. A Cox Proportional Hazards model was developed to compare the rate of failure among the procedures. There were 340 THC studies. The catheters were managed as follows: 93 patients received conservative management only, 15 had a guidewire advanced through the catheter, 147 underwent catheter exchange, 62 were treated with a fibrin stripping procedure, and 23 received a thrombolytic infusion. Estimated 30-day patency rates for THCs were 38.2% for conservative management, 30.9% for guidewire manipulation of catheter tip, 53.6% for catheter exchange, 76.1% for fibrin stripping, and 69.8% for thrombolytic infusion. Differences among the treatments were observed (p < 0.01) and pairwise comparisons were made among the treatment groups. Failure rates were significantly higher in the catheter exchange (p <0.01) and guidewire manipulation at catheter tip (p <0.01) groups when compared with the fibrin stripping group. The catheter exchange and guidewire manipulation groups also experienced higher rates of failure when compared with the thrombolytic infusion group, although the differences were not statistically significant (p = 0.08, p = 0.17, respectively). Four procedure-related complications requiring hospitalization or other intervention occurred. Three of these were in the catheter exchange group with one incidence of sepsis, one drug reaction, and one hematoma. Fibrin stripping and thrombolytic infusion provided the greatest efficacy in the treatment of poorly functioning THCs, but all therapies demonstrated wide-ranging results. Central line exchanges did not provide a superior secondary patency and experienced more complications.