This study analyzed the effect of Arbidol, a broad-spectrum antiviral compound, on the outcomes of COVID-19 patients. Records of 252 COVID-19 patients were retrospectively analyzed from February 13 to February 29, 2020 in 4 inpatient wards in the Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. The rate of clinical improvement was significantly greater among patients treated with Arbidol than among those who did not receive Arbidol (86.8% vs. 54.2%). In moderately and severely ill patients, the clinical improvement rates in the Arbidol group were 95.6% and 81.7%, respectively, which was significantly higher than in the no-Arbidol group (66.6% and 53.8%). Among critically ill patients, however, there was no significant difference. The levels of hypersensitive C-reactive protein, lactate dehydrogenase, D-dimer, IL-6, and IL-10 were increased in non-improved patients but declined during treatment in the improved patients. This suggests these mediators are associated with the disease severity and could potentially serve as prognostic markers. Moreover, our data demonstrate that Arbidol is effective in the treatment of COVID-19 patients and may serve as a cost-effective antiviral treatment strategy for patients with moderate to severe COVID-19 symptoms.