Prescription rates and attendant costs of proton pump inhibitors (PPIs) continue to rise. The aim of this study was to assess the extent and appropriateness of PPI prescribing in an Irish general hospital. Using a structured pro forma, we conducted a 1-day comprehensive survey of the prescription charts of all inpatients. Of the 157 inpatients, 48 (30.6%) were on PPI therapy and omeprazole was the most widely prescribed PPI. Rabeprazole, the least expensive PPI, was the least prescribed. Prescription of PPI therapy was for an approved indication in 32 patients (66.6%) but was for an unapproved or unknown indication in 16 (33.3%). Prescribing had been initiated in hospital in 34 patients (70.8%) but only one-third of the patients on PPI therapy had undergone endoscopy. Over 90% of patients were on additional, often multiple, prescribed medications. Our results suggest that PPIs are overprescribed in hospital practice, and there is scope to improve the quality and cost-effectiveness of PPI prescribing.