Aim Proton‐pump inhibitors (PPI) are extensively prescribed worldwide. However, little information is available on PPI prescribing patterns, associated clinical and demographic factors, and potential drug–drug interactions in frail older patients. Methods Data on clinical and demographic characteristics, and full medication exposure were collected in a consecutive series of 361 older patients (age 84 ± 7 years) admitted to two acute geriatric admission units (Aberdeen, National Health Service Grampian) between 1 February 2010 and 30 June 2010. A set of predetermined criteria was used to assess appropriateness of PPI prescribing. Results PPI were prescribed in 148 patients (41.0%). Inappropriate overprescribing was observed in 127 patients (35.2% of the study population, 85.8% of patients prescribed PPI). PPI were inappropriately not prescribed in 20 patients (48.8% of patients with an indication for PPI treatment). Regression analysis showed that the total number of non‐PPI prescribed drugs (OR 1.08; 95%CI 1.01–1.15) and a higher Charlson Comorbidity Index (OR 1.08; 95%CI 1.001–1.16) were independently associated with inappropriate PPI overprescribing. Potential drug–drug interactions were found in 75 patients (22.8% of the study population), mainly in patients with PPI overprescribing. Conclusions Inappropriate PPI prescribing is common in frail older hospitalized patients, and might increase the risk of drug–drug interactions. Polypharmacy and comorbidity were independently associated with inappropriate PPI prescribing in this group. Geriatr Gerontol Int 2013; ●●: ●●–●●.