To assess changes in Medicare payments for neovascular age-related macular degeneration (AMD) since introduction of anti-vascular endothelial growth factor (VEGF) therapies. Retrospective, longitudinal cohort study. Using the Medicare 5% sample, beneficiaries with new diagnoses of neovascular AMD in 1994 (N = 2497), 2000 (N = 3927), and 2006 (N = 6041) were identified using International Classification of Diseases (ICD-9-CM). The total first-year health care and eye care costs were calculated for each beneficiary. Propensity score matching was used to match individuals in the 2000 and 2006 cohorts with the 1994 cohort on age, sex, race, Charlson Comorbidity Index, and low vision/blindness. The number of beneficiaries newly diagnosed with neovascular AMD more than doubled between the 1994 and 2006 cohorts. Overall yearly Part B payments per beneficiary increased significantly from $3567 for the 1994 to $5991 for the 2006 cohort (P < .01) in constant 2008 dollars. Payments for eye care alone doubled from $1504 for the 1994 cohort to $3263 for the 2006 cohort (P < .01). Most of the increase in payments for eye care in 2006 reflected payments for anti-VEGF injections, which were $1609 over 1 year. Mean annual numbers of visits and imaging studies also increased significantly between the 1994 and 2006 cohort. Results were similar in the matched sample. The introduction of anti-VEGF intravitreal injections has offered remarkable clinical benefits for patients with neovascular AMD, but these benefits have come at the cost of an increased financial burden of providing care for these patients.