Elevated D-dimer and other markers of coagulation disturbances are predictors of severity and mortality in COVID-19 patients and heparin use during hospital stay has been associated to a decreased mortality. Similar findings have been described in other coronaviruses. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting intravascular coagulation as a prominent feature of organ failure and of the acro-ischaemia increasingly reported in these patients. In COVID-19 pulmonary compliance is preserved despite severe hypoxemia, contrarily to classic ARDS, corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure in these patients. Based on this rationale, a series of 27 consecutive COVID-19 patients admitted to our hospital were treated with heparin in doses tailored to clinical severity, ranging from 1 - 2 mg/kg of enoxaparin BD. PaO2/FiO2 ratio increased significantly over the 72 hours following the start of anticoagulation, from 254(SD 90) to 325(SD 80), p=0.013, and over half of the patients were discharged home within an average time of 7.3 (SD 4.0) days. Half of mechanically ventilated patients were extubated within 10.3 (SD 1.5) days. The remaining patients showed progressive, albeit slower improvement, and both the mortality and the bleeding complications rate in these patients were absent. Even though this uncontrolled case series does not offer absolute proof of DIC as the underlying mechanism of respiratory failure in COVID-19, as well as patients positive response to tailored dose heparinization, it contributes to the understanding of the physiopathological mechanism of the disease and provides valuable information for the treatment of these very sick patients while we await the results of further prospective controlled studies.