OBJECTIVES: Potentially inappropriate prescribing (PIP) is an extensive and persistent problem in elderly populations globally and has been associated with negative health outcomes. We successfully implemented a 3-year proof-of- concept study, featuring a multifactorial, general practitioner-focused intervention designed to decrease PIP in the older population in the Local Health Authority (LHA) of Parma, Emilia-Romagna region (RER), Italy. We investigated whether the observed reduction of PIP due to the intervention was associated with a decrease of unplanned hospitalizations. METHODS: Using the RER administrative healthcare database, we performed a retrospective analysis of all approximately 1.5 million RER elderly patients (≥ 65 years). We compared PIP exposure and unplanned hospitalizations in the elderly patients of Parma LHA versus the rest of the RER between the pre-intervention period (1/1/2005-12/31/2007) and post-intervention period (1/1/2008-9/30/2011). PIP exposure was defined as the dispensing of a medication that “should always be avoided” based on the 2007 Maio criteria.  A hospitalization was attributed to PIP if it occurred during an exposure period. We estimated the hazard ratio of PIP-related hospitalizations in the pre- and post-intervention periods using a time-dependent Cox proportional hazards model adjusted for age, sex, and history of hospitalizations and disease complexity in the preceding year.  We also estimated the number of hospitalizations avoided due to the intervention using the preventable fraction equation. RESULTS: After adjustment, the risk of PIP-related hospitalization post-intervention was 7% less than pre-intervention (HR 0.93; CI 0.89, 0.97) in Parma LHA with respect to the rest of the RER during that period.  In the post-intervention period, an estimated 411 PIP-related hospitalizations were avoided in Parma LHA attributable to the intervention (95% CI: 169-674). CONCLUSIONS: Our physician-targeted PIP quality intervention significantly decreased the risk of unplanned hospitalizations.  These results stress the need for further development of interventions to reduce PIP exposure in elderly patients.