This study aimed to assess whether repetitive intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) cause sustained elevation of intraocular pressure (SE-IOP). We conducted a systematic review and meta-analysis based on five randomized controlled trials (RCTs) assessing 1428 subjects and 17 non-RCTs evaluating 8358 cases. In the RCTs, an increased risk of SE-IOP was found in the anti-VEGF group (summary risk ratio [RR] = 3.00, 95% confidence interval [CI]: 1.63–5.53) compared with the sham injection or laser group. The increased risk of SE-IOP was correlated with follow-up duration (RR = 2.14, 95% CI 0.69–6.57 at 6 months; RR = 3.15, 95% CI 0.99–10.09 at 12 months; RR = 3.48, 95% CI 1.38–8.78 at 23 months). The risk of SE-IOP after non-exclusion of pre-existing glaucoma patients (RR = 3.48, 95% CI 1.38–8.78) was higher than that obtained after excluding pre-existing glaucoma patients (RR = 2.6, 95% CI 1.16–5.81). In non-RCTs, the pooled prevalence of SE-IOP was 4.7% (95% CI 3.7–5.8) regardless of diagnosis criteria. In conclusion, repeated intravitreal injections of anti-VEGF agents cause a 2-fold elevation in SE-IOP risk.