OBJECTIVES: A systematic review and network meta-analysis (NMA) to compare the relative effectiveness of intravitreal aflibercept (IVT-AFL), intravitreal ranibizumab (IVR), dexamethasone, and sham in patients with macular edema secondary to central retinal vein occlusion (ME/CRVO). METHODS: A comprehensive systematic literature review was conducted to identify randomised clinical trials (RCTs) of IVT-AFL 2 mg, IVR 0.5 mg, and dexamethasone 0.7 mg in ME/CRVO. The main outcome was the proportion of patients gaining ≥15 letters from baseline; additional outcomes included mean change in best-corrected visual acuity and the proportion of patients losing ≥15 letters from baseline. A Bayesian NMA was conducted to analyse data extracted from the selected RCTs and estimate the efficacy of IVT-AFL against the other active treatments using sham as the common reference treatment. Odds ratios (OR) and credible intervals (CrI) were calculated using fixed-effect (FE) and random-effects (RE) models. RESULTS:  Five RCTs with a total sample size of 1471 patients were included in the analysis. Study designs and baseline characteristics were comparable. All RCTs had sham as a comparator and reported data after a randomised period of 24 weeks. For the proportion of patients gaining ≥15 letters from baseline, IVT-AFL was superior to dexamethasone (OR, 5.01; 95% CrI, 2.14–1.63) and sham (OR, 7.7; 95% CrI, 4.62–13.14), but not significantly superior to IVR (OR, 1.69; 95% CrI, 0.78–3.68) (FE model). For the other outcomes, IVT-AFL was also superior to sham and dexamethasone; however, the results did not achieve statistical significance against IVR. Results were similar between the FE and RE models. CONCLUSIONS:  In this indirect analysis, IVT-AFL was more effective than dexamethasone and sham in improving visual acuity outcomes at Week 24 in ME/CRVO patients. No significant differences were found between IVT-AFL and IVR at Week 24.