Background Proton pump inhibitors are among the most widely prescribed drugs in the world, but more than half of the indications for prescription are unjustified. The misuse of this therapeutic class has heavy consequences such as additional health costs, adverse drug reactions following long-term use and gastric acid rebound when the proton pump inhibitor is discontinued. Objective The overprescription of proton pump inhibitors is therefore becoming a public health problem, which led us to evaluate their use within the Geneva University Hospitals. Setting Patients hospitalized in two divisions of the department of internal medicine of the Geneva University Hospitals on a single day. Methods This is a register-based cross-sectional study and it collected data about the prescription pattern of proton pump inhibitors by consulting the electronic records of patients included. Main outcome measure To determine if the proton pump inhibitors prescription is made according to the market authorization and the available guidelines. Results Hundred-eighty patients were included. 54% of patients were on proton pump inhibitors, 29% of whom had their treatment initiated at hospital. Of the indications for treatment, 72% were not justified and 63% of the justified indications did not have an adequate dosage. Therefore, in all patients with a proton pump inhibitor at hospital, only 11% had a justified indication with an adequate dose. Finally, 87% of known home prescriptions were renewed on admission and among them, 71% did not have a justified or possibly justified indication according to the guidelines. Conclusion Indication for treatment inside the hospital was not justified in 72% of patients and only 11% had a justified indication with an adequate dosage. Precise guidelines with evidence-based indications and adequate daily doses would help to correctly prescribe proton pump inhibitors. Moreover, patients should benefit from a thorough evaluation of their treatment.