Vitamin K antagonists are the most widely used form of long-term treatment of patients with venous thromboembolism (VTE). In certain patients, however, the desire to initiate oral anticoagulant therapy is tempered by concern about the risk of bleeding. In these cases, consideration should be given to alternative forms of treatment. Unfractionated heparin (UFH) may be an alternative, but it requires twice-daily subcutaneous administration, and the dosage must be adjusted after periodic blood tests. Therapy with low-molecular-weight heparin (LMWH) is the likely practical solution to this dilemma. Up to now, four small randomized trials have compared the efficacy and safety of LMWH therapy as an alternative to oral anticoagulants. When the results of the four studies are combined, a significant decrease is found in the bleeding rate in patients receiving LMWH. Two further studies by our group confirm this lower bleeding rate in patients on LMWH therapy. According to these data, we suggest that LMWH could be an alternative to oral anticoagulants in patients who cannot attend the laboratory for prothrombin time monitoring, as well as those who are at high risk for bleeding.