OBJECTIVES: The ex-factory price of pharmaceutical drug interventions in the United States is generally greater than those in Europe and the rest of world, with some instances of U.S. price differences exceeding 200-250%. As such, the U.S. House of Representatives investigative panel is mounting continuous pressure on manufacturers to review the rising cost of prescription drugs and associated cost to patients. Resulting from a fragmented multi-stakeholder healthcare system consisting of both private and public payers, the U.S. payers have limited negotiating power, although the Affordable Care Act has allowed for the utilization of the Independent Payment Advisory Board (IPAB) to review prices. Given other markets have been successful at employing international reference pricing (IRP) to control their prices, a similar approach may be useful for Medicare in lieu of IPAB. METHODS: Navigant’s ‘Pricing and Revenue Optimization For International Launch Excellence’ (PROFILE) Model has been utilized to illustrate the impact of IRP on U.S. price development, with respect to other global markets. Price development was analyzed for a given therapeutic class, assessing impact of various reference baskets including: (1) EU5, (2) top-5 GDP ex-U.S. and (3) Neighboring markets to U.S. (e.g. Canada). Price evolution was assessed over a 10 year horizon, with IRP assumed after 18 months of baseline price changes. RESULTS: The model demonstrates the inclusion of IRP within the U.S. controls the ex-factory prices across a 10 year horizon. Baskets containing the lower-priced markets were most successful at managing price. In addition, inclusion of IRP prevented the year-over-year price increases typically seen in the current environment. CONCLUSIONS: Assuming legislative interest in implementing IRP, the U.S. government may reduce the differential pricing existing between U.S. and other markets. However, as the U.S. is typically a first-launched market, price control may only be achieved following re-referencing.