AIM To evaluate the characteristics of the prescription of the proton pump inhibitor drugs(PPI) and the adherence to the indications of the guidelines regulating thereimbursement limitations set forth by the Italian Drug Agency.METHODS Thirty general practitioners(GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs(PPI users) and non-users(PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules. RESULTS Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs(NSAIDS), acetylsalicylic acid(ASA), oral anticoagulant therapy(OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease(8.5%) and for the protection of gastric damage caused by NSAIDS(6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT. CONCLUSION A substantial number of patients who apparently do not