Background: Biosimilars have the potential to reduce healthcare costs for payers and provide savings to patients by introducing competition and driving down prices. Centers for Medicare and Medicaid Services’ (CMS) Average Sales Price (ASP) is used as an index price to determine Medicare drug reimbursement (MCR) in the United States and is published on a quarterly basis. We studied the trends of ASP and MCR reimbursement rates for reference and biosimilar agents. Methods: Using publicly available quarterly CMS data, we evaluated and compared the trends of MCR for 7 reference and 25 biosimilar agents for a period of 2 years before and 5 years after launch. We evaluated the MCR for filgrastim, pegfilgrastim, bevacizumab, trastuzumab, rituximab, infliximab, epoetin-alfa, and their respective biosimilars. Results: On average, the published MCR for all reference agents increased by 9.2% (range: 0.6% to 16.8%) over the 2-year period prior to the biosimilar launch. Over the 5-year period following the launch of the first biosimilar, reference agents’ MCR fell 32.7% (range: -8.0% to -78.0%) while biosimilar agents’ MCR fell 50.3% (range: -3.7% to -90.5%) over the same period, with a median follow-up period of 16 quarters. Biosimilar MCR rates fell at an accelerated rate compared to reference agents. 76% (19 of 25) of the biosimilars that entered the market had an initial MCR below, and 20% (5 of 25) above, that of the reference agent. 16 of 18 successive biosimilars for reference agents launched with a MCR above that of the first biosimilar. Despite the fall in MCR, reference agents’ rates in the most recent quarter were 2x higher than their corresponding biosimilar agents, except for pegfilgrastim, which had a precipitous fall in MCR (87%) after biosimilar launch to a price lower than 5 of its 6 biosimilars. Conclusions: Biosimilars, with lower Medicare reimbursement at launch, and an accelerated decline in ASP post-launch, deliver on the goal of driving lower healthcare costs and increased savings. Biosimilar competition breaks the price increase trends with reference agents and contributes to a decrease in reference agent drug reimbursement. The effects of manufacturer rebates, payer policies, 340b programs, and discounts on ASP and Medicare reimbursement are also areas of active investigation.