OBJECTIVE The purpose of this study was to compare the efficacy and safety of treating mobile iliofemoral patients with deep venous thrombosis (DVT) with subcutaneous low-molecular-weight heparin (dalteparin sodium) either 200 IU/kg once-daily (group 1) or 100 IU/kg twice-daily (group 2). METHODS Consecutive patients with suspected iliofemoral DVT diagnosed by duplex ultrasonography and verified by radionuclide venography were randomized to one of the two low-molecular-weight heparin (LMWH) regimens. Perfusion and when necessary ventilation scans were performed for diagnosis of pulmonary emboli (PE) in all patients immediately after admission and were repeated after approximately 10 days, whereupon oral anticoagulation was started unless contraindicated. Minimal and maximal anti-factor Xa activity was measured after 2 to 3 days of therapy. All patients were kept mobile with compression bandages. The primary end point was reduction in frequency of PE as assessed on the second lung scan. RESULTS A total of 140 patients with confirmed DVT were randomized, 76 to group 1 and 64 to group 2. The two groups were comparable in their baseline clinical characteristics. In the initial lung scans 36 (47.4%) patients in group 1 and 29 (45.3%) patients in group 2 had objectively verified PE, but only 11 (14.5%) and 8 (12.5%) patients, respectively, had symptoms. After dalteparin treatment PE disappeared in two patients in group 1, but in two other cases new PEs occurred, (NS). In group 2 a resolution of PEs was observed in eight patients, whereas only one new PE could be detected. This change reflects the efficacy of therapy as defined by resolution of existing PEs and by the occurrence of new PEs and is statistically significant according to McNemar's chi-square test with the exact binomial method pair procedure (p < 0.05). Symptomatic PE was reduced from 14.5% to 5.3% in group 1 (96% to CI for the difference, -1.5% to +17.3%) and from 12.5% to 1.6% in group 2 (95% CI for the difference 0.7% to 18%, p < 0.05). There was one single fatal PE, one serious and three minor bleeding episodes in group 1, and one minor bleeding episode in group 2 (95% CI for the difference: -3.6% to +8.1%). CONCLUSIONS Treatment of ambulant iliofemoral patients with DVT with 100 IU/kg dalteparin twice-daily appears to be moe safe and effective than 200 IU/kg given once-daily. Bed rest is not necessary for treating mobile patients.