OBJECTIVES: Anti-VEGF therapy improves visual acuity in patients with neovascular (“wet”) age-related macular degeneration (wAMD). By comparing different treatment regimen scenarios, based on data from available randomized clinical studies, the objective was to compare costs for intravitreal aflibercept (IVT-AFL) treatment with Ranibizumab treatment when treating wAMD patients in a Spanish setting. METHODS: A Markov model, describing wAMD treatment was estimated, calculating the direct medical costs based on 2-year clinical trial data. Parameters were estimated from trial data, published literature, and expert opinion. Costs, discounted at 3% per year, were calculated over a five-year horizon. Alternative scenarios and deterministic sensitivity analyses were performed and reported. RESULTS: IVT-AFL, dosed every two months in Year 1 and modified quarterly dosing in year two, was least expensive, €13,519, followed by IVT-AFL every second month, for two years, €16,085. Cost of Ranibizumab monthly (RBZ Q4) regimens ranged from €17,284 (12.6 injections over two years) to €26,457 (monthly injections over two years). Results were driven by less frequent IVT-AFL dosing and monitoring. The model was most sensitive to RBZ Q4 Year 1 efficacy and Year 2 injection frequency. CONCLUSIONS: IVT-AFL is less expensive than Ranibizumab when treating wAMD in Spain, due to less frequent dosing with IVT-AFL and lower monitoring costs.