OBJECTIVES: Prevalence of potentially inappropriate prescribing (PIP) of harmful medications in the elderly has been widely investigated, but it remains unclear whether PIP is predictive of adverse events. Our study objective was to determine whether exposure to PIP is linked to increased rates of hospitalization and mortality. METHODS: We performed a retrospective analysis using the Italian Regione Emilia-Romagna (RER) longitudinal administrative healthcare database of all elderly patients (≥ 65 years) from 2003 to 2013. The RER database includes de-identified, fully-linkable demographic, hospital, and pharmacy claims data for all residents in the region. PIP exposure initiated upon the dispensing of a medication that “should always be avoided” based on the Maio criteria. To estimate PIP exposure we computed the number of days supplied for each medication of interest (using Defined Daily Doses) plus 30 days. An exposure period spanned the duration of consecutive PIP dispensings. An event, the composite outcome of hospitalization or death, was attributed to PIP if it occurred during an exposure period. Rate ratios and 95% confidence intervals (CI) were estimated by Poisson generalized estimating equations modeling. RESULTS: The 1,471,179 elderly individuals living in the RER contributed a total of 10,369,120 person-years (PY) of follow-up time and experienced a total of 1,973,878 events. The unadjusted event rate was 1.572 (95% CI: 1.562, 1.580) times greater among patients exposed to PIP compared to those not exposed (2.87 events/10 PY vs. 1.82 events/10 PY). The unadjusted mortality rate was 1.473 (95% CI: 1.458, 1.488) times greater with PIP exposure (0.51/10 PY vs. 0.35/10 PY). CONCLUSIONS: These results indicate that exposure to PIP may be associated with higher hospitalization and mortality rates in elderly patients. This analysis, using a large cohort of patients, sheds light on the importance of reducing PIP in this population.