OBJECTIVES: To estimate the prevalence of clinically important potential drug-drug interactions (DDIs) among residents of Regione Emilia Romagna (RER), Italy. METHODS: We conducted a retrospective cohort study using the 2004 outpatient prescription claims database of RER, which was linked to the 2004 demographic file of 4,222,165 RER residents. Using a previously published list of clinically important potential DDIs as framework, we identified 11 potential DDIs that could be captured through the RER database because both drugs were reimbursed by the 2004 Italian National Formulary. A potential DDI was defined as the presence of a minimum 5-day overlap in days supply for each of the drugs in an interacting pair. The World Health Organization Anatomical Therapeutic Classification/Defined Daily Dose System was used to determine a proxy measure of days supply for each drug. The one-year prevalence of each potential DDI was quantified at the patient level. RESULTS: In 2004, the 11 potential DDIs occurred 7,379 times in 6,681 RER residents, yielding a one-year prevalence of 158.2 cases per 100,000 individuals. The mean age of those exposed to potential DDIs was 74.1 (SD=10.8) years and about 52% were female. Of those exposed, 559 (8.4%) were exposed to 2 potential DDIs and 64 (1.0%) were exposed to at least 3 potential DDIs. The most commonly identified potentially interacting medication pairs were warfarin and nonsteroidal anti-inflammatory drugs (5,616 cases), theophylline/aminophylline and the fluoroquinolones ciprofloxacin and fluvoxamine (759), warfarin and barbiturates (530), and warfarin and fibric acids (339). CONCLUSION: To our knowledge, this is the first large population-based study in Italy documenting the prevalence of potential DDIs. A substantial number of clinically important potential DDIs were identified, particularly among warfarin users. DDIs are predictable, hence preventable. Awareness of the most commonly occurring potential DDIs can help practitioners prevent coadministration of these potentially dangerous medication combinations.