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Introduction: Proton pump inhibitor (PPI) prescriptions have raised concern for both huge increase of health expenditure and possible long-term adverse effects., Objective: To evaluate appropriateness of PPI prescription in ambulatory and hospital care., Design: Observational cohort study., Patients: Patients admitted to the Internal Medicine Unit of Bologna S. Orsola Hospital between 15/09/2013 and 15/12/2013. Data on clinical condition and drug therapy were collected at three time points: admission (reflecting GP's prescription), hospital stay and discharge., Main Measures: Appropriateness of PPI use was evaluated as follows: (1) agreement between PPI use/non-use and appropriate clinical condition; (2) in PPI users, assessment of Medication Appropriateness Index (MAI). Differences in appropriateness among time points were analyzed by chi-square test. Logistic regression model was used to identify possible determinants of PPI appropriateness., Key Results: Among 280 patients, 56% received PPI at least once in the three time points. Appropriateness, according to indication of use, was similar between admission and hospital stay (61% vs. 62%; p=0.82) and between hospital stay and discharge (62% vs. 59%; p=0.94). MAI score showed important, although statistically non-significant, change in appropriateness between admission and hospital stay (20% vs. 28%; p=0.16). Age≥65 was always associated with appropriate PPI use (up to OR=4.37; p<0.01), whereas cardiovascular comorbidity and conditions requiring analgesic treatment influenced appropriateness only at admission (OR=3.84; p<0.01 and OR=0.34; p<0.01, respectively)., Conclusions: Hospital clinicians only rarely reconsidered GP's choice to prescribe PPI. Room for improvement in PPI appropriateness is represented by (1) assessing gastrointestinal risk in each patient under analgesics and anti-inflammatory drugs, and (2) short-term re-evaluation of PPI prescription after discharge., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)