Background: the use of proton pump inhibitors (PPI) has increased substantially during the last years, possibly due to a significant proportion of prescriptions that do not follow the approved indications. Objective: to assess the prevalence of PPI prescription and the appropriateness of the prescription within the Emergency Department (ED) of a Spanish university hospital. Materials and methods: a cross-sectional, retrospective prescription-indication drug-use study was performed, which selected 384 patients that presented to the ED over two days in January 2016. Results: of the total cohort, 23.2% were taking PPI before their hospital visit and only 20.2% had a correct indication and dosage; 2.9% of the patient cohort had an indication for PPI treatment but had not been prescribed them. A drug other than omeprazole was used in 25% of cases; 30.47% of the patients were discharged with a PPI and only 28.2% of them had the correct indication and dosage. Finally, 5.7% were not prescribed PPI even though it was warranted. PPI prescription increased with age whereas the indication for the prescription decreased. Furthermore, the use of these drugs was higher in hospitalized patients compared to discharged patients. Conclusions: these results are in line with similar studies, which demonstrate the existence of an over-prescription of PPI. PPI prescription needs to be improved, thereby reducing drug interactions, adverse effects and unnecessary economical expenses.