Background Intravitreal injection (IVI) is a standard procedure performed in ophthalmology to treat several conditions, and is performed in different settings across countries. The Italian guidelines recommend this intervention is performed in an operating room to minimize the risk of infections, while in other countries, including Canada, USA and the UK, IVIs are performed in the ophthalmologist's office. The 2020 COVID-19 outbreak caused a dramatic modification in outpatient care. Consequently, non-urgent surgical activities, like IVIs, were subjected to a drastic reduction. Methods We conducted observational study which investigated the outcomes of IVIs performed in an ophthalmologist's office using a mobile laminar flow unit, the Operio mobile (Toul Meditech, Operio®) versus an operating room setting. Results Use of the Operio mobile allowed the safety performance of 3838 IVIs during COVID-19 and significantly reduced the waiting time of the first visit. This results in a faster intervention without affecting the technical IVI procedure that remained unchanged comparing the two settings. Specifically, we observed a 26% reduction in operation costs for each IVI performed in the office, which can be translated to a higher impact when considering the total number of IVIs performed over one year. Conclusion The use of the Operio mobile in an ophthalmologist's office provides flexibility to perform IVIs, assuring patient safety, reducing healthcare personnel employment times, and the waiting lists for the patients, increasing the number of surgeries and improving the cost-effectiveness of the procedure.