Beside the anticoagulant and antithrombotic activity, heparin also exerts a lipolytic activity. In a prospective study on patients with venous thromboembolism and some contraindications to coumarin therapy, a low-molecular-weight heparin (Fragmin®) was compared to unfractioned (UF) heparin in terms of both efficacy and safety. A secondary aim was to study the influence of both types of heparin on serum lipid levels. Sixty-six consecutive patients who were not taking concomitant treatment with lipid-lowering drugs entered the study. Patients received treatment with either UF heparin, 10,000 IU s.c, b.d., or Fragmin 5,000 IU anti-factor Xa s.c, b.d. for a period of 3 or 6 months, according to whether the initial diagnosis was deep venous thrombosis or pulmonary embolism. Each patient was followed up at 6-weekly intervals, and blood samples were obtained at discharge, and then 6 and 12 weeks after discharge. Finally, a further sample was obtained 3 months after therapy was discontinued. Total cholesterol levels increased significantly in both groups of patients: levels increased from 193 ± 56 to 246 ± 63 mg/dl in the UF heparin group (p < 0.001), and from 189 ± 53 to 222 ± 47 mg/dl in the Fragmin group (p < 0.05). The increase was mostly due to a very strong increase in HDL cholesterol levels in patients receiving UF heparin (from 46 ± 12 to 71 ± 23 mg/dl; p < 0.000005). Three months after discharge, HDL cholesterol levels were significantly higher in patients taking UF heparin than in patients in Fragmin (p = 0.006). By contrast, patients on Fragmin exhibited a significant increase in LDL cholesterol levels: from 112 ± 39 to 139 ± 37 mg/dl;