BACKGROUND: A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, the application of heparin in COVID-19 has been recommended by some expert consensus due to the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. METHODS: Coagulation results, medications and outcomes of consecutive patients being classified as severe COVID-19 in Tongji hospital were retrospectively analysed. The 28-day mortality between heparin users and nonusers were compared, also in different risk of coagulopaphy which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result. RESULTS: There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin, LMWH) for 7 days or longer. The D-dimer, prothrombin time and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference on 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P=0.910). But the 28-day mortality of heparin users were lower than nonusers In patients with SIC score >/=4 (40.0% vs 64.2%, P=0.029), or D-dimer > 6 fold of upper limit of normal (32.8% vs 52.4%, P=0.017). CONCLUSIONS: Anticoagulant therapy mainly with LMWH appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.