AIM: To assess the effect of lens status on sustained intraocular pressure (IOP) elevation in patients treated intravitreally with anti-vascular endothelial growth factor (VEGF) agents. METHODS: Data were retrospectively collected for all patients treated with intravitreal injections of anti-VEGF medication at a tertiary medical center in July 2015. Findings were analyzed by lens status during 6 months’ follow-up. The main outcome measure was a sustained increase in IOP (≥21 mm Hg or change of ≥6 mm Hg from baseline on ≥2 consecutive visits, or addition of a new IOP-lowering medication during follow-up). RESULTS: A total of 119 eyes of 100 patients met the study criteria: 40 phakic, 40 pseudophakic, and 39 pseudophakic after Nd:YAG capsulotomy. The rate of sustained IOP elevation was significantly higher in the post-capsulotomy group (23.1%) than in the phakic/pseudophakic groups (8.1%; P=0.032), with no statistically significant differences among the 3 groups in mean number of injections, either total (P=0.82) or by type of anti-VEGF mediation (bevacizumab: P=0.19; ranibizumab: P=0.13), or mean follow-up time (P=0.70). CONCLUSION: Nd:YAG capsulotomy appears to be a risk factor for sustained IOP elevation in patients receiving intravitreal anti-VEGF injections. This finding has important implications given the growing use of anti-VEGF treatment and the irreversible effects of elevated IOP.