AbstractTeicoplanin has a potential antiviral activity expressed against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and was suggested as a complementary option to treat coronavirus disease 2019 (COVID‐19) patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID‐19 in critically ill patients. Fifty‐five patients with severe COVID‐19, hospitalized in the intensive care units (ICUs) and treated with best available therapy were retrospectively analysed. Among them 34 patients were also treated with teicoplanin (Tei‐COVID group), while 21 without teicoplanin (control group). Crude in‐hospital Day‐30 mortality was lower in Tei‐COVID group (35.2%) than in control group (42.8%), however not reaching statistical significance (p = .654). No statistically significant differences in length of stay in the ICU were observed between Tei‐COVID group and control group (p = .248). On Day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei‐COVID group and 57.1% of control group, without statistical difference. Serum C‐reactive protein level was significantly reduced in Tei‐COVID group compared to control group, but not other biochemical parameters. Finally, Gram‐positive were the causative pathogens for 25% of BSIs in Tei‐COVID group and for 70.6% in controls. No side effects related to teicoplanin use were observed. Despite several limitations require further research, in this study the use of teicoplanin is not associated with a significant improvement in outcomes analysed. The antiviral activity of teicoplanin against SARS‐CoV‐2, previously documented, is probably more effective at early clinical stages.