Objectives: Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting. Methods: Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up prior to completion of treatment were excluded. Consecutive sampling technique was employed. The patients who received bilateral anti-VEGF injections were analysed separately from the ones who received unilateral injections. All injections were administered in operating theatre setting. The rate of endophthalmitis was measured in each group. Results: A total of 30,258 injections were administered of which 15,338 were bilateral injections. Four cases (4/30,258, 0.013%) of endophthalmitis occurred during the study period. Only one case (1/15,338, 0.0065%) of endophthalmitis occurred after the administration of simultaneous bilateral anti-VEGF injections. Conclusions: Administration of simultaneous bilateral anti-VEGF injections was safe in our population. doi: https://doi.org/10.12669/pjms.38.8.5125 How to cite this:Jeeva IK, Masud S, Siddiqui MAR, Fahad HM. Safety of simultaneous bilateral intravitreal versus unilateral anti-vasculo-endothelial growth factors injection in an operating room setting. Pak J Med Sci. 2022;38(8):---. doi: https://doi.org/10.12669/pjms.38.8.5125 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.