The coronavirus disease 2019 (COVID-19) has formed a global pandemic since late 2019. Benefit from the application experience of Chinese Medicine (CM) for influenza and SARS, CM has been used to save patients at the early stage of COVID-19 outbreak in China. In order to evaluate the efficacy and safety of CM, and comparing with that of Western Medicine (WM) for COVID-19, we conducted a retrospective case series study based on the patients in Wuhan Jinyintan Hospital, Wuhan, China. The inclusion and exclusion criteria of data extraction was set for this retrospective study. All patients who were admitted by the Wuhan Jinyintan Hospital between January 17 and February 25, 2020 were considered. In addition, patients enrolled met the severe defined by the guidelines released by the National Health Commission of the People's Republic of China. In these cases included in the study, CM or WM treatment was selected according to the wishes of the patients at the beginning of hospitalization. The patients in CM group was treated with Huashi Baidu granule (137 g po, bid) combined with the injections of Xiyanping (100 mg iv, bid), Xuebijing (100 ml iv, bid) and Shenmai (60 ml iv, qd) according to the syndrome of epidemic toxin blocking the lung in the theory of Traditional Chinese Medicine. The WM group received antiviral therapy (including abidor capsule 0.2 g po, tid; Lopinavir-Ritonavir tablets, 500 mg po, bid), antibiotics (such as cefoperazone, 2 g iv, bid; moxifloxacin hydrochloride tablets, 0.4 g po, qd) or corticosteroid therapy (such as methylprednisolone succinate sodium, 40 mg, iv, 40 mg, qd; prednisone, 30 mg po, qd). In addition, patients in both groups received routine supportive treatment, including oxygen inhalation, symptomatic therapy, and/or human intravenous immunoglobulin, and/or serum albumin, and therapy for underlying diseases. The clinical outcomes were evaluated based on changes before and after the treatment related with clinical manifestations, computer tomography (CT) scan images, and laboratory examinations. 55 severe COVID-19 patients, with 23 in CM group and 32 in WM group, were included for analyzed. There was no case of death, transferred to ICU, or received invasive mechanical ventilation in two groups during hospitalization. The median time of SARS-CoV-2 RNA clearance in CM and WM group were 12 days and 15.5 days (P = 0.018). Further, the chest CT imaging showed more widely lung lesion opacity absorbed in the CM group (P < 0.05). The C-reactive protein level, erythrocyte sedimentation rate, serum ferritin, and myoglobin decreased significantly in the CM group (P < 0.05). There was no significant difference in adverse events in terms of liver function and renal function between the two groups. Based on this retrospective analysis from Wuhan Jinyintan Hospital, CM has better effects in SARS-CoV-2 RNA clearance, lung lesion opacity absorbed and reduced inflammation in severe COVID-19 patients, is effective and safe therapy for treating severe COVID-19 and reducing mortality. Copyright © 2021. Published by Elsevier B.V.