The over-prescription of proton pump inhibitors (PPIs) has become a global clinical issue. We conducted a retrospective study to investigate the trend in PPI prescriptions in a general hospital in Japan and propose the proper use of PPIs with official indications. This study included inpatients at a general hospital between December 2017 and March 2018 who were prescribed oral PPIs (lansoprazole, esomeprazole, and vonoprazan). A pharmacist reviewed electronic medical records (such as referral letters from other hospitals and current medical history) for each extracted patient to see if they met the criteria and divided them into two categories, "appropriate use" and "inappropriate use." The criteria for "appropriate use" were defined as official indications and generally accepted off-label uses. A pharmacist reviewed the survey results. The primary outcome was the percentage of inappropriate use of oral PPIs among patients. Of the 334 eligible patients, 39% used oral PPIs inappropriately. Logistic regression analysis showed that "age" and "esomeprazole” were factors contributing to inappropriate use. The rate of inappropriate use of oral PPIs in Japan is as high as that in other countries. The reasons for inappropriate use vary between Japan and other countries. This should be examined in more detail in future studies, as no statistically significant difference was found in the number of concomitant medications between the appropriate and inappropriate use groups. The off-label use of esomeprazole for the treatment of eosinophilic esophagitis and nonsteroidal anti-inflammatory drug-induced gastric ulcers has been reported.