BACKGROUND: Critically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state. The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e. D-dimer). We also evaluated the impact of different doses of low molecular weight heparin (LMWH) on the incidence of bleedings. METHODS: The data of forty-two patients admitted to the Intensive Care Unit (ICU) were retrospectively analyzed. On ICU admission, patients with D-dimer<3000ng/mL (Group 1) received enoxaparin 4000 UI (6000 UI, if body mass index >35) subcutaneously b.i.d. and patients with D-dimer>/=3000ng/mL (Group 2) received enoxaparin 100UI/kg every 12h. Aspirin was administered to all patients once a day. RESULTS: Both groups presented a high incidence of perivascular thrombosis (40.9% in Group 1 and 30% in Group 2). Patients of Group 2 suffered a higher incidence of venous thromboembolism (VTE) than Group 1 (65% vs 13.6%, p=0.001). One patient (4.5%) of Group 1 and three patients (15%) of Group 2 suffered from minor bleeding; no patient had major bleeding. Group 2 had a longer ICU and hospital stay than Group 1 (11.5+/-5.6 vs 9.0+/-4.8 and 30+/-4.9 vs 21+/-2.3, p<0.05, respectively) as well as increased ICU mortality (25% vs 9.1%). CONCLUSIONS: More severe critically ill COVID-19 patients have a high incidence of VTE and worse outcome, despite the use of heparin at the therapeutic dose. However, the use of heparin did not increase the incidence of bleeding complications.