Background: This study aims to evaluate the antimicrobial prescribing practices in hospital settings in Italy, focusing on the appropriateness of antibiotic use. Methods: This study was carried out through a retrospective review of medical records of patients admitted in three public hospitals located in Campania Region (Italy) between 1 January and 31 December 2018. Results: More than one third (34.2%) of patients received at least one inappropriate antibiotic prescription (antibiotic administered and not indicated). Being female, having a >1 Charlson comorbidity index score, and having a longer hospital stay were significant determinants of an inappropriate antibiotic prescription. Instead, patients who had had a non-urgent hospital admission, an infection on hospital admission, and a microbiological culture test during hospital stay were significantly less likely to have an inappropriate prescription. When the antibiotic prescriptions were analyzed, in 26.6% of cases they were not indicated, while among the 687 antibiotic prescriptions with indication, incorrect choice of antibiotics (36.8%) was the most common reason of the inappropriateness. Conclusions: The findings of the study indicate that the inappropriate use of antibiotics continues to be a relevant issue in the hospital setting and specific interventions are needed to encourage a wider utilization of diagnostic tools to practice targeted therapies and to counter the antimicrobial resistance.