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Objective To assess the prevalence of potential drug-drug interactions (pDDIs) among polypharmacy patients in Jordan using Lexicomp®. Additionally, this study aims to categorize and rate the identified pDDIs according to interaction risk, severity, and reliability. Methods A descriptive cross-sectional study was conducted at six different hospitals representing different public health sectors in Jordan (ministry of health, royal medical services, and university-affiliated hospitals). Polypharmacy patients from outpatient clinics (e.g., c