PurposeTo evaluate long-term effects of multiple intravitreal anti- vascular endothelial growth factor (VEGF) injections on intraocular pressure (IOP) in eyes with neovascular age-related macular degeneration (AMD) or retinal vein occlusion (RVO). DesignRetrospective cohort study. MethodsThis study enrolled patients who underwent multiple (more than three) intravitreal anti-VEGF injections and who were followed for more than 12 months after their last injection. IOP elevation was defined as an increase of 5 mmHg over the baseline measurement on two consecutive visits. The frequency of IOP elevation was determined. A hazard ratio of each putative risk factor for IOP elevation was calculated using the Cox proportional hazard model for the total participants, incorporating underlying disease as a covariate, as well as for each cohort. ResultsSix-hundred and twenty-nine eyes with neovascular AMD and 95 eyes with RVO were included in the analysis. Twenty eyes with neovascular AMD (3.0%) and 7 eyes with RVO (7.4%) experienced IOP elevation after multiple anti-VEGF injections, with an overall incidence of 3.7%. In the Cox proportional hazard analysis of total participants, a diagnosis of RVO (3.424, P = 0.005), a history of glaucoma (8.441, P = 0.001), and low baseline IOP (0.865, P = 0.040) were all significant risk factors for IOP elevation after multiple anti-VEGF injections. ConclusionA history of multiple intravitreal anti-VEGF injections was not a significant risk factor for IOP elevation in our study. IOP elevation was more common in eyes with RVO than with AMD after anti-VEGF injection.