A group of 105 consecutive patients with venographically proved major acute deep vein thrombosis (DVT) were randomized in an open prospective study to evaluate the comparative efficacy and safety of a fixed dose of subcutaneous low-molecular-weight heparin (LMWH) and warfarin for the prevention of recurrent venous thromboembolism. Four patients developed venographically proved recurrent DVT during the 3 months of treatment: three in the LMWH group and one in the warfarin group. Nonfatal pulmonary embolism occurred in two patients in the LMWH group and in one in the warfarin group. Five of the 55 patients (10%) in the warfarin group and none of the 50 patients in the LMWH developed bleeding complications (two-tailed Fisher exact test, p = 0.06). A preliminary assessment of the costs indicated that treatment with LMWH was less expensive by Pounds 900 per patient than warfarin. In conclusion, the fixed daily dose of LMWH and the adjusted dose of warfarin therapy were of similar efficacy in preventing recurrence of DVT. However, warfarin therapy, despite strict laboratory control, is associated with more frequent side effects and is expensive. Another study with a higher dose of LMWH is recommended.