PURPOSE: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12- and 24-months in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! PROJECT: PARTICIPANTS: Treatment-naive eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5mg], aflibercept [2mg] or bevacizumab [1 mg]) with at least 3 injections, from December 2013 to 31 December 2018 and at least 12 months of follow-up. METHODS: IOP was measured at each clinical visit for all eyes as part of routine practice. MAIN OUTCOME MEASURES: The primary outcome was the mean change in IOP (mmHg) at 12-months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. RESULTS: We identified 3429 treatment-naive eyes (395 bevacizumab, 1138 aflibercept and 1896 ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean [95%CI] IOP change was -0.5 [-0.6, -0.3] mmHg at 12 months and -0.4 [-0.6, -0.3] mmHg at 24 months while the proportion of clinically significant IOP increases were 5.6% and 8.8%. A lower mean IOP change and fewer IOP elevations at 12- and 24-months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (for both comparison P