Objectives To evaluate the efficacy and safety of prophylactic anticoagulant treatment in the primary prevention of venous thromboembolism in patients with central venous catheters (CVC). Data Sources MEDLINE (1964-2004), EMBASE (1980-2004), Current Contents, Premedline, the Cochrane Controlled Trials Registry (2004), ACP Journal Club (2003), the Database of Reviews of Effects (2003), and the Cochrane Database of Systematic Reviews (2004) were searched using truncated keyword searches for thrombosis, anticoagulation, and central venous catheterization. Article retrieval was supplemented by crosschecking bibliographies of relevant studies. Study Selection All prospective studies of adult patients receiving systemic anticoagulant prophylaxis compared with a concurrent control group and with outcomes evaluated using venograms and/or duplex ultrasonography were selected for review. Retrospective studies, review articles, case reports, and studies evaluating dialysis patients were excluded. Data Extraction Two reviewers independently assessed each article using predefined criteria for study validity and recorded efficacy and safety results. A third reviewer resolved disagreements by adjudication. Data Synthesis Thirteen studies were evaluated. Eight studies were randomized controlled trials. Only three studies found a significant absolute risk reduction (ARR) in deep vein thrombosis using prophylactic anticoagulation: 55.3% ARR with 2500 IU daily of dalteparin, 28.0% ARR using 1 mg of warfarin daily, and 11.1% ARR using continuous infusion of heparin at 1000 IU/kg/day. No study met all of the predefined criteria for adequately evaluating safety. Conclusion Limited data from randomized controlled trials suggest that heparin dalteparin and warfarin are effective in the prevention of DVT in patients with CVC. Bleeding risk cannot be precisely estimated from the available data. The efficacy and safety of anticoagulant prophylaxis should be evaluated by randomized trials of sufficient size to make valid conclusions.