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Background To evaluate the possible effects of multiple intravitreal anti-vascular endothelial growth factor (VEGF) injections on intraocular pressure (IOP). Methods This study included 50 eyes of 50 patients who underwent multiple (≥ 10 injections) intravitreal anti-VEGF injections in one eye with age-related macular degeneration, diabetic macular edema or retinal vein occlusion. IOP was recorded after every injection on the first postoperative day. IOP > 21 mmHg was regarded as abnormal. For statistical analysis, the IOP was correlated with the number of injections. Results A total of 669 IOP-measurements (mean 13.4 treatment/eye) were analyzed. No IOP-elevation was recorded in 43 eyes (86%). Transient elevated IOP > 21 mmHg was measured after 19 intravitreal injections (2.8%, one patients with 8 IOP elevations). In general, there was no increasing risk of IOP elevation with time, no case of sustained IOP elevation and no additional long term glaucoma treatment necessary. Eyes with pre-existing glaucoma were significantly more affected from transient IOP-elevation than non-glaucoma eyes (5.5 vs. 2.2%). Conclusions Multiple anti-VEGF injections are not associated with an increased risk of sustained IOP-elevation. On the other hand, individual risk factors exist and predispose to IOP-elevation (e.g., pre-existing glaucoma).