OBJECTIVES: To evaluate the cost-effectiveness of intravitreal aflibercept (IVT-AFL) versus intravitreal ranibizumab for the management of neovascular age-related macular degeneration (nAMD) in Greece. METHODS: A Markov “better-eye-treated” model consisting of 6 health states (5 states related to vision impairment, and death) was adapted in the Greek healthcare setting to compare monthly (2q4) and  bimonthly (2q8; following 3 monthly loading doses) treatment with 2 mg IVT-AFL with 0.5 mg ranibizumab either on a monthly basis (0.5q4) or as needed (PRN). The time horizon of analysis was 20 years. All patients were assumed to discontinue treatment at the end of the second year. Clinical inputs and utility values were extracted from the literature. The analysis was conducted from a payer perspective and, as such, only costs reimbursed by the payer were considered (in 2014 euros). Costs and outcomes were discounted by 3.5% per year. The primary outcomes were costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio per QALY gained. Probabilistic sensitivity analysis (PSA) was conducted. RESULTS: IVT-AFL 2q8 was the least expensive regimen (€21,930) while ranibizumab 0.5q4 was the most expensive (€26,203). For all regimens, the total cost was driven mainly by the direct nonmedical costs, followed by drug acquisition costs. In terms of QALYs, IVT-AFL 2q4 was the most efficacious (4.057), while IVT-AFL 2q8 was more efficacious (4.049) than ranibizumab PRN (4.025) but less efficacious than ranibizumab 0.5q4 (4.052). Although IVT-AFL 2q4 was more efficacious than IVT-AFL 2q8, the former cost approximately €350,000 per QALY gained compared with the latter. Both ranibizumab regimens were deemed inferior. PSA revealed that at all willingness-to-pay thresholds up to €335,000, IVT-AFL 2q8 had the highest probability of being cost-effective compared with the other treatment strategies. CONCLUSIONS: Bi-monthly treatment with IVT-AFL may be the most cost-effective option for the treatment of nAMD in Greece.