BACKGOUND: The drug central monitoring system set up in Italy to evaluate the real-time trends of medicines used in hospital and primary care settings contributed to inform drug supplies, avoided stockpiling and allowed to monitor adherence to clinical practice guidelines for the treatment of COVID-19 patients. The primary objective of the study is to understand how and to what extent the drug utilisation tracked the evolution of COVID-19 pandemic and evaluate the different pharmacological approaches adopted in hospital and primary care settings. METHODS: A national ecological study correlating the drug utilisation of specific categories of drugs related to SARS-CoV-2 with the number of SARS-CoV-2 hospitalised or positive subjects. The correlation is estimated by using linear regression models and reporting the angular coefficients (slope) with relative p value. RESULTS: Overall, 15 drug categories are identified: 7 categories are available in both settings, 6 categories are prevalent in hospital setting and 2 categories are used in primary care. As for drugs common to both settings, a statistically significant positive association between the number of SARS-CoV-2-positive subjects and drug consumption is found only for low-molecular-weight heparin, oxygen, azithromycin and steroids. As regards drugs used exclusively in hospital, a significant correlation is observed for cardiac stimulants, general anaesthetics, hypnotics and sedatives as well as muscle relaxant drugs. Among drugs used exclusively in primary care, the study has shown a positive correlation only for vitamin D. Finally, the adoption in clinical practice of the recommendations issued by the competent authorities was assessed: at hospital level, the use of drugs with a negative recommendation (such as hydroxychloroquine and azithromycin) was promptly stopped. CONCLUSIONS: Study findings show a positive correlation between the use of specific drug categories used during the pandemic and the number of COVID-19-positive and hospitalised patients, suggesting the relevant role of evaluating drug utilisation patterns in tracking the evolution of pandemics and guideline adherence in clinical practice.