BACKGROUND: The increasing demand for intravitreal injections (IVIs) necessitates exploring efficient and safe alternatives to traditional operating rooms (OR). The use of portable laminar airflow (LAF) devices has emerged as a potential solution for creating a sterile environment for IVIs outside of the OR. This study investigates the safety outcomes of using the Operio mobile LAF device to perform IVIs in a non-OR setting. METHODS: This retrospective study included 1420 patients who received a total of 6638 IVIs between January 2021 and December 2024 at the Ospedale Fatebenefratelli Isola Tiberina - Gemelli Isola in Rome, Italy. The Operio mobile LAF device was positioned beside the operating table, directing airflow towards the surgical area. A standardized protocol was followed for patient preparation, anaesthesia, IVI administration, and post-injection care. The primary outcome was the incidence of endophthalmitis. RESULTS: Anti-vascular endothelial growth factor (anti-VEGF) agents constituted 96% of the total injections (6369/6638). Corticosteroids accounted for the remaining 4% (269/6638). One case of endophthalmitis after an injection of Mvasi was observed among the 6638 IVIs (0.015%) administered during the study period. Other complications, such as subconjunctival haemorrhage (386 eyes) and transient ocular hypertension (57 eyes), were not linked with the use of Operio device. CONCLUSION: Using a portable LAF device, such as the Operio mobile, for IVIs in a non-OR setting is a safe and effective alternative to traditional ORs.