OBJECTIVES In Turkey, a medicine reference pricing system has been in use since 2004. The price of pharmaceuticals is determined by the acceptance of the lowest ex-factory price in the reference countries (Greece, France, Italy, Portugal, Spain). We aimed to examine the first 100 medicine’s, having the annual maximum amount on the average Turkish Lira (TL) based medicine sales between the years 2008-2013 which have 25.1% value in the total pharmaceutical market, reference price changes in these period. METHODS While pharmaceutical sales data were obtained from the IMS Health-Turkey data base, medicine prices were obtained from the Medicine Price List published by Turkish Medicines and Medical Devices Agency. RESULTS In 2008, the top 100 medicines in determining the price of most of Italy were taken as the reference country, followed by Spain and Greece. In 2013 while Greece is taken as the reference country more common; France and Italy are to follow. In 2008, only one medicine’s price increased, and only one medicine’s price decreased because of the reference price. In 2009 and 2010 price increases did not seen. In 2009, 8 and in 2010, 30 medicines prices had decreased. In 2011, 2012 and 2013 totally 27 medicines reference prices had increased. 21 medicine’s price in 2011, 20 medicine’s price in 2012 and 24 medicine’s price in 2013 had decreased. While mostly France (13 medicines) connected to the reference price increases, mostly Greece (58 medicines) has been based reference price drop in the analyzed period. CONCLUSIONS The application of reference prices, medicine prices to be reduced to a large extent. Greece based reference price decreases are observed to be mainly from the year 2010. The reason for this is considered as the economic crisis in Greece and the agreement with the IMF, EU and ECB, the Greek government at cost-containment.