Aging is associated with an increase in the prevalence of chronic diseases and polypharmacy, and with the prescription of potentially inappropriate medications (PIMs). This study aimed to analyze the variation in PIMs from hospital admission to discharge. A retrospective cohort study was conducted on inpatients of an internal medicine service. According to the Beers criteria, 80.7% of the patients had been prescribed at least one PIM at admission and 87.2% at discharge; metoclopramide was the most-prescribed PIM from admission to discharge, and acetylsalicylic acid was the most-deprescribed one. According to the STOPP criteria, 49.4% of patients had been prescribed at least one PIM at admission and 62.2% at discharge; quetiapine was the most-prescribed PIM from admission to discharge, and captopril was the most-deprescribed one. According to the EU(7)-PIM list, 51.3% of patients had been prescribed at least one PIM at admission and 70.3% at discharge, and bisacodyl was the most-prescribed PIM from admission to discharge and propranolol the most-deprescribed one. It was found that the number of PIMs at discharge was higher than at admission, suggesting the need to develop a guide with adapted criteria to be applied in an internal medicine service.