Objective: To evaluate the cost-effectiveness of monthly and as-needed dosing protocols using ranibizumab or bevacizumab for the treatment of neovascular age-related macular degeneration (AMD), when the treatment costs of severe ocular and systemic adverse events are considered. Methods: A Markov model was developed to assess the cost effectiveness of each of the following protocols: monthly ranibizumab, monthly bevacizumab, as-needed ranibizumab and as-needed bevacizumab. Direct costs and utilities were assessed from the perspective of a third-party payer or an insurance company. Cost effectiveness was evaluated in 2011 US dollars per quality-adjusted life year (QALY). Results: Considering the treatment costs of severe medical and ocular adverse events, the cost effectiveness of each protocol is as follows: monthly ranibizumab $63,333/QALY, ranibizumab as needed $18,571/QALY, bevacizumab monthly $2,676/QALY and bevacizumab as needed $3,333/QALY. Sensitivity analysis of the treatment costs of medical and ocular adverse events demonstrated minimal impact on relative cost-effectiveness. Conclusion: At current prices, monthly bevacizumab is the most cost-effective anti-VEGF AMD treatment protocol. Ranibizumab is as cost effective as bevacizumab at a maximum price of $158 per dose.