Bloodstream infections related to the use of central venous catheters are an important cause of patient morbidity, mortality, and increased health care costs. Catheter-related infection may be due to fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. This study was a randomized, controlled trial in which 246 patients with nontunneled central venous catheters were randomly assigned to receive a heparin-coated catheter with 50 mL/d of normal saline solution as a continuous infusion (heparin-coated group) or a noncoated catheter with a continuous infusion of low-dose unfractionated heparin (control group: continuous infusion of 100 U/kg/d). Catheter-related bloodstream infection occurred in 2.5% (3/120 catheters) in the heparin-coated group (0.9 events per 1,000 days) and in 9.1% (11/120 catheters) in the control group (3.5 events per 1,000 days; P = 0.027). No other risk factors were found for the development of catheter-related bloodstream infection. Six and seven patients experienced severe bleeding in the heparin-coated and control groups, respectively (P = 1.00). We did not observe heparin-induced thrombocytopenia. The use of heparin-coated catheters can be a safe and effective approach to the prevention of catheter-related bloodstream infection in patients with hematooncologic disease.