Catheter-related bacteremia, a frequent complication in patients who are undergoing hemodialysis, may be prevented by eradication of the catheter biofilm. Catheter lock solution (CLS) is an investigational preparation containing taurolidine, a biocompatible antimicrobial agent, and citrate, an anticoagulant agent. CLS was instilled into the catheter lumens after each dialysis session for 20 catheter-dependent hemodialysis patients. Catheter outcomes were compared with those observed in 30 concurrent control patients whose catheters were instilled with heparin. Bacteremia-free survival at 90 days was higher among patients who received CLS than among control patients who received heparin (94% vs. 47%; P < .001). Unassisted catheter patency (without tissue plasminogen activator instillation) was lower among patients who received CLS than among control patients (32% vs. 76%; P < .001). CLS dramatically reduces the frequency of catheter-related bacteremia among patients undergoing hemodialysis, although there is an increased requirement for thrombolytic interventions to maintain catheter patency.