OBJECTIVES: In some European Union countries in recent years the use of proton pump inhibitors (PPIs) has greatly increased. In march 2006 in Italy lansoprazole came off patent and became a relatively cheap treatment. Several national and regional measures to rationalise PPIs spending growth were taken to promote the choice of less expensive PPI, lansoprazole, regardless of his antisecretory potency. The goal of this study was to compare general practitioners’prescription  (GPs) of different PPIs and explore how GPs PPI prescribing changes following the loss of lansoprazole patent. METHODS: We extracted all records of PPI prescribing within a General Practitioner Research Database of 99 GPs located in Naples, Italy, and analysed them using Microsoft SQL Server 2005. All records for patients who had been prescribed a PPI were divided into calendar years from 2005 to 2007 (the year prior to and following lansoprazole generic). PPI consumption were quantified using Defined Daily Dose system (DDD). RESULTS: The total volume of PPI’s prescribing increased steadily over the 3 years. The proportion of defined daily doses accounted for by lansoprazole was 11.8% in 2005 rising to 35.9% in 2007. The contribution of omeprazole, the most often PPI prescribed, to total PPIs prescriptions decreased from 43.0% to 22.7% in the same period, while esomeprazole contribution remained costant. Following the loss of patent, new lansoprazole prescriptions increased substantially; 32.7% of subjects switched from another PPI to lansoprazole. CONCLUSIONS: To reduce costs GPs have been coming under pressure encouraging the prescription of a cheaper drug. The wide variation in PPI prescribing suggests that the choice of PPI by GPs was distorted by the effect of lansoprazole “liberalization”.