OBJECTIVE: The recent outbreak of SARS-CoV-2 infection in Italy has resulted in a sudden and massive flow of patients into emergency rooms, and a high number of hospitalizations with the need for respiratory isolation. Massive admission of patients to the Policlinico “Agostino Gemelli” Foundation of Rome, Italy, determined the need for reengineering the entire hospital. MATERIALS AND METHODS: In this article, we consider some of the structural and organizational changes that have been necessary to deal with the emergency, with particular reference to non-intensive medicine wards, and the preventive measures aimed at limiting the spread of SARS-CoV-2 infection among hospital staff and patients themselves. RESULTS: 577 staff members were subjected to molecular tests in 1-month period and 3.8% of the total were positive. 636 patients admitted to the COVID-19 pathway were included and analyzed: 45.4% were identified as SARS-CoV-2 positive. More SARS-CoV-2 negative patients were discharged in comparison to SARS-CoV-2 positive patients (59% vs. 41%, respectively). On the other hand, more SARS-CoV-2 positive patients were transferred to ICUs in comparison to SARS-CoV-2 negative patients (16% vs. 1%, respectively). Occurrence of death was similar between the two groups, 11% vs. 7%, for SARS-CoV-2 negative and positive patients, respectively. 25% of ≥80 years old SARS-CoV-2 positive patients died during the hospitalization, while death rate was lower in other age groups (5% in 70-79 years old patients and 0% in remaining age groups). CONCLUSIONS: Rapid hospital reengineering has probably had an impact on the management of patients with and without SARS-CoV-2 infection, and on in-hospital mortality rates over the reporting period.