OBJECTIVES: In May 2011, the Portuguese government signed a Memorandum of Understanding with the EC, ECB and IMF as part of a financial rescue program.  Part of the program involved a reduction of € 50M in the public expenditure with pharmaceuticals. One specific measure introduced a new margin scheme to pharmacies (and distributors), consisted of an increasing fixed fee and a regressive margin as a percentage of the ex-factory price, making prices lower in general. Prior to this margin scheme, a linear system was in place. This measure will clearly affect the pharmaceutical retail sectors, with a decrease in the pharmacies’ profits. In this study we assess the impact of the several measures aimed at decreasing pharmaceutical expenditure on the profitability of the Portuguese pharmacies, namely administrative and voluntary price reductions and if pharmacies can support the change in the margin scheme.  METHODS: We use a sample of 383 pharmacies, with data from the sales of each different transaction. The time span considers the period from January to May in both 2011 and 2012.  RESULTS: Using transaction-level data, the analysis allows for the simulation of new and old margins, keeping consumption constant. Estimates regarding savings for patients and for payers (mainly the National Health Service), and impact on retail and wholesale distributors can be traced. In particular, we address issues such as whether small pharmacies are harder hit than large ones, and whether particular groups of patients (eg. Old pensioneers) benefit more or less than the majority of the population. Due to the new margins design, patients benefit, though payers (especially the National Health Service) also benefit.  CONCLUSIONS: The new remuneration system is likely to produce the expected savings. Special attention should be given to harder-hit pharmacies and patient access to medicines and pharmacy services.