OBJECTIVES: International reference pricing (IRP), also known as External Reference Pricing (ERP), is a cost-containment method used internationally to contain drug expenditure. The USA is currently looking to implement IRP. This study aims to estimate the impact on treatment costs of five products by comparing the US wholesaler acquisition cost (WAC) with two possible US IRP scenarios. METHODS: Five products were taken for price per mg and treatment cost per month analysis with their current FDA, EMA and Japanese recommended dosages (taken from labels and authorisation review materials). Prices for drugs were taken from the Rx Price Index^TM and from health authority websites. Two country baskets were run in the analysis; the first using countries from the Prescription Drug Price Relief Act (EU5, CA, JP), the second adding the Nordics (DK, NO, SE), Greece and the Netherlands. Estimated US IRP prices included a 26% additional premium as per the government’s proposal. RESULTS: Estimated cost per treatment month using calculated US IRP across either scenario and every product resulted in savings of between 9-74% compared with estimated WAC price per treatment month. When taking the Medicare/Medicaid public drug spends for these products, we found that there was an estimated 60-70% saving when using the calculated US IRP versus the WAC price. CONCLUSIONS: The analysis shows that should the US implement an IRP model, prices for drugs would decrease resulting in substantial Medicare/Medicaid savings. However, as the US is typically one of the first product launch markets, IRP information may not be available. The German method whereby it acts as a free market for the first 12 months and then reviews the price based on IRP may be a relevant model for the USA to adopt.