Objective To systematically review the efficacy of intravitreal injection of anti-vascular endothelial growth factors (anti-VEGF) on macular edema (ME) secondary to retinal vein occlusion (RVO). Methods Databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data and VIP were electronically searched to identify randomized controlled trials on different anti-VEGF drugs in the treatment of RVO-ME from inception to September 17th 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of the included studies. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 11 RCTs were included. Data from these studies included 2 436 eyes, of which 1 682 involved central retinal vein occlusion and 754 involved branch retinal vein occlusion. The results of meta-analysis showed that at 6 months of follow-up, anti-VEGF drug treatment of RVO-ME improved corrected visual acuity (MD=14.97, 95%CI 10.09 to 19.86, P<0.000 01) and reduced central retinal thickness (MD= −218.21, 95%CI −295.56 to −140.86, P<0.000 01) compared with control groups. At 12 months, anti-VEGF treatment of RVO-ME showed better improvement in corrected visual acuity compared with control group (MD=5.70, 95%CI 3.90 to 7.50, P<0.000 01). No statistically differences were observed in the improvements corrected visual acuity with different anti-VEGF drugs. However, for central retinal vein occlusion, different anti-VEGF drugs improved the central retinal thickness including aflibercept vs. bevacizumab (MD=−46.79, 95%CI −83.12 to −10.46, P=0.01), and bevacizumab vs. ranibizumab (MD=76.03, 95%CI 30.76 to 121.30, P=0.001) had significant differences. Conclusions The current evidence shows that anti-VEGF drugs can improve vision and reduce macular edema in the treatment of RVO-ME. Bevacizumab may be an effective alternative to ranibizumab or aflibercept. Existing evidence cannot determine differences between the improvement of best-corrected vision and the reduction of central retinal thickness during the long-term treatment of RVO, which requires to be verified by further research.