||The aim of this study was to determine the prevalence of potential drug-drug interactions (pDDIs), to identify drugs frequently involved in interaction and to identify factors associated with pDDIs in medical wards of Tikur Anbessa Specialized Hospital (TASH). A prospective crossectional study was conducted on 163 patients admitted in medical wards of TASH. Presence of interaction was cheeked using medscape drug-drug interaction checker. Data was analysed using SPSS version 21. A test of association was done using binary and multiple logistic regressions. The overall prevalence of potential drug-drug interaction was 86.5%. Interactions of major severity account for about one fifth of total pDDIs. The number of drugs taken by the patient was found to be significantly associated with pDDIs. The study highlighted the need to carefully select drugs and implement active pharmaceutical care services in order to prevent harmful effect of these interactions.