Objectives: Proton pump inhibitors (PPI) are the most effective drugs in the treatment of acid-related gastrointestinal disorders. Yet, many studies reported potential adverse drug reactions associated with long-term use. In order to reduce the rates of inappropriate PPI prescriptions and to improve patient safety, a tool aimed at guiding pharmacists to analyze PPI prescriptions was designed. It results in a thesaurus of clinical situations designed to argue about the inappropriateness of some PPI prescriptions and to highlight the risk associated with them. Methods: Clinical situations in which PPIs are inappropriate were identified by four pharmacists in one gastroenterological, one surgery/liver transplantation, one internal medicine and one oncology units. A scientific literature search was performed for each clinical situation in order to corroborate the pharmacist interventions. Results: The thesaurus comprises two parts, the first one is dedicated to 12 clinical situations in which a PPI is not required (acute pancreatitis, cholecystectomy etc.), while the second one focus on 22 situations in which PPIs are associated with specific adverse drug reactions (Clostridium difficile infection, vitamin deficiency etc.). Eighty-one articles were used to support the pharmacist interventions. Conclusion: This thesaurus is an analysis tool aimed at guiding pharmacists identify and argue about the inappropriateness of some PPI prescriptions in order to convince doctors to discontinue or not to initiate PPI prescriptions.