OBJECTIVES: To evaluate the cost-effectiveness of intravitreal aflibercept compared with ranibizumab and bevacizumab for wet age-related macular degeneration (AMD) patients. METHODS: A Markov model was applied in cost-utility analysis to evaluate the incremental cost-effectiveness ratio (ICER) between aflibercept, ranibizumab, and bevacizumab from societal perspective over 12 years. Patients switched to as-needed based dosing after one year on the FDA approved regimens. Yearly transitional probabilities were obtained and extrapolated from two-year randomized control trials. Direct medical costs, resource utilization and utility scores were estimated and calculated using the Medicare National Physician Fee Schedule and other published studies. Costs were adjusted and reported in 2013 US dollar. Base case was a 78 year-old patient with vision acuity at 60-letter level. The cost-effectiveness threshold was $ 51,749, as three-fold GDP per capita in 2013. One-way sensitivity analyses were performed to test for the robustness of the model.    RESULTS: The cost-effectiveness ratio (CER) for aflibercept, ranibizumab, and bevacizumab were $31,404, $34,888, 43,096, respectively. The ICER for aflibercept was dominant compared to both ranibizumab and bevacizumab. When caregiver costs were excluded, bevacizumab became the cost-effective treatment (dominated by ranibizumab; the ICER for aflibercept was $73,625). The number of as-needed doses, instruments used for obtaining utility, initial level of vision acuity level and variation in drug costs demonstrated small impact on relative cost-effectiveness. CONCLUSIONS: Aflibercept was the cost-effective treatment for AMD patients compared to ranibizumab and bevacizumab from societal perspective.