To analyze Medicare Part B spending on anti-vascular endothelial growth factor (VEGF) medications.Observational cohort study using Medicare Part B claims data released by the Centers for Medicare and Medicaid Services.Medicare Part B beneficiaries and their providers.Data from 2011 through 2015 were used to analyze intravitreal injection claims for ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY).Number of intravitreal injections performed annually, Medicare Part B expenditures on anti-VEGF medications, and beneficiary cost share.The number of Medicare Part B claims for ranibizumab decreased from 671 869 in 2011 to 573 796 in 2015. During this 5-year period, associated Medicare drug costs averaged $1.3 billion annually. The number of Medicare Part B claims for aflibercept increased from 518 836 in 2013 to 866 749 in 2015. Annual Medicare drug expenditure for aflibercept was $1.4 billion on average. On average, Medicare spent $9719 and $9934 annually on each beneficiary receiving ranibizumab and aflibercept injections, respectively.The number of anti-VEGF injections performed annually, and their associated costs, continue to rise. Ranibizumab and aflibercept costs account for 12% of the Medicare Part B budget annually. Bevacizumab represents a substantially more cost-effective alternative, but its use can present many obstacles, including efficacy concerns, dependence on compounding pharmacies, and off-label usage.