Objective To assess the incidence and type of potential, clinically significant drug-drug interactions in elderly outpatients with arterial hypertension. Setting Three community pharmacies in Croatia. Method Eligible patients were aged 65 or older, treated for arterial hypertension and received 2 or more drugs. Potential interactions were identified by Lexi-Interact software. The software categorized each potential interaction according to clinical significance in five groups: (A) No known interaction; (B) Specified agents may interact, but there is little to no evidence of clinical concern; (C) Specified agents may interact in a clinically significant manner. Monitoring therapy is suggested; (D) The two medications may interact in a clinically significant manner. Modification of therapy is suggested; (X) Contraindicated combination. Interactions of level C, D and X were considered clinically significant. Main outcome measure The incidence and type of potential drug-drug interactions. Results There were 265 patients included in the study. Potential, clinically significant drug interactions were identified in 240 (90.6%) patients, out of which 97.9% had interactions with clinical significance C, 20.4% D, and 0.8% X. The median number of drug interactions per patient was 4. We identified 215 drug combinations with the potential to cause clinically significant interaction, out of which 83.3% had clinical significance C, 16.3% clinical significance D, and 0.4% clinical significance X. Conclusion Drug-drug interactions are common in elderly hypertensive patients. Computer-based screening could help pharmacists and physicians to recognize potential, clinically significant interactions.