Background COVID-19 is a respiratory disease associated to thrombotic outcomes with coagulation and endothelial disorders . Based on that, several anticoagulation (AC) guidelines have been proposed . We aimed to identify if AC therapy modifies the risk of developing severe COVID-19 . Methods and Results COVID-19 patients initially admitted in medical wards of 24 French hospitals were included prospectively from February 26th to April 20th , 2020 . We used Poisson regression model, Cox proportional hazard model and matched propensity score to assess the effect of AC on outcomes (intensive care unit (ICU) admission and/or in-hospital mortality). Study enrolled 2878 COVID-19 patients, among whom 382 (13.2 %) were treated with oral AC therapy prior to hospitalization . After adjustment, AC therapy prior to hospitalization was associated with a better prognosis with an adjusted Hazard Ratio (aHR) 0.70 (95% CI 0.55-0.88). Analyses performed using propensity score matching confirmed that AC therapy prior to hospitalization was associated with a better prognosis with an aHR of 0.43 (95% CI 0.29-0.63) for ICU admission and aHR of 0.76 (95% CI 0.61-0.98) for composite criteria ICU admission and/or death . In contrast, therapeutic or prophylactic low or high dose AC started during hospitalization were not associated with any of the outcomes . Conclusions AC therapy used prior to hospitalization in medical wards was associated with a better prognosis in contrast to AC initiated during hospitalization . AC therapy introduced in early step of disease could better prevent COVID-19-associated coagulopathy, endotheliopathy and prognosis.