In France, efforts to optimize prescribing of proton-pump inhibitors (PPIs) are rare. Various studies have shown that the prescription of these drugs is excessive. This has consequences regarding costs and iatrogenesis. The objective of this study was to describe the type of drug related problems (DRP) and pharmaceutical interventions reported by pharmacists practicing in a university hospital. Methods: Drug related problems and pharmaceutical interventions (PI) made, were recorded on a database. They were classified according to the grid code of the French Society of Clinical Pharmacy. Results and discussion: Over a 3 years period, 132.890 prescriptions were analysed. 15.347 generated PI. Among them 701 (4.6%) concerned PPIs. Most frequently reported problems were: lack of indication or patients without a documented indication (24.4%), drug-drug interactions (22.4%) and inappropriate route or mode of administration (19.8%). Discontinuation has been proposed in 40.5% of cases, followed by substitution (22.0%) and dosage titration (17.3%). Physicians modified the prescription according to 51.3% of PI. The main PI, discontinuation therapy, is associated with over-prescription of this drug class. Nevertheless, the rate of DRP recorded (0.5%) is low compared to the high exposure of patients on PPIs and misuse (or overuse?) reported in the literature. Conclusion: PI made during the analysis of prescription contributes to rationalizing the use of PPIs. The action of the pharmacist must be strengthened through training of health professionals, and communication strategies to improve practices.