OBJECTIVES:  Anti-VEGF therapy with ranibizumab (RBZ) dosed monthly improves visual acuity over time in patients with neovascular (“wet”) age-related macular degeneration (wAMD). In two identical phase 3 trials, IAI dosed every 2 months, following 3 initial monthly doses demonstrated clinically equivalent efficacy and a similar safety profile to RBZ0.5mg dosed monthly (RBZQ4). We assessed U.S. cost effectiveness of IAI 2Q8 compared with RBZ Q4 in treating wAMD.    METHODS: A Markov model was developed to characterize treatment with IAI 2Q8 and RBZ Q4 over two years. Patients move among health states based on visual acuity in the better-seeing eye. The model assumed patients discontinue treatment when vision drops below 20/400; ten percent were assumed to be treated in both eyes. The model calculated direct medical costs (drug, administration, monitoring, vision impairment and adverse events) and quality adjusted life-years (QALYs). Model parameters were estimated from clinical trial data, published literature, or expert opinion.  Cost-effectiveness was reported through incremental cost-effectiveness ratios (ICERs) for a 2-year horizon. Costs and outcomes were discounted 3% per year. Deterministic and probabilistic sensitivity analyses were performed.  RESULTS: Treatment with IAI 2Q8 cost $30,700 over two years, compared with $54,300 for RBZ Q4. Treatment cost was the largest cost component, comprising 78% and 85% of total costs of the IAI and RBZ regimens, respectively. Both regimens resulted in similar QALY gains (1.124 for IAI, 1.125 for RBZ).  Compared with IAI, RBZ cost nearly $26 million per QALY gained. The model was most sensitive to unit drug cost and utility weights. IAI was dominant in 41% of PSA iterations. CONCLUSIONS: In treating wAMD, IAI 2mg dosed every 2 months, following 3 initial monthly doses is less expensive than monthly RBZ. Both demonstrate similar efficacy.  Of the two, IAI is the cost-effective alternative at conventional willingness to pay thresholds.