OBJECTIVES: To assess the incidence, nature and severity of potential drug-drug interactions (pDDIs) in renal impairment patients admitted in nephrology ward of a tertiary care hospital in Pakistan. METHODS: A retrospective data of 200 renal impairment patients was obtained conveniently from a tertiary care hospital and evaluated to observe the incidence, nature and severity of pDDIs using Medscape drug interaction checker software [http://reference.medscape.com/drug-interactionchecker]. All of the statistical analysis was carried out using SPSS version 16. RESULTS: In total, 659 pDDIs were observed in 180 (90.0%) renal impairment patients giving a median value of 2 (IQR=4) with a range of 1-15 pDDIs per patient. Of those 659 pDDIs, around 10.9% were serious, 59.2% were significant, 3.8% were contraindicated, and nearly 26.1% of pDDIs were minor in severity. Furthermore, nearly 45.2% pDDIs were pharmacokinetic, 38.7% pharmacodynamic, 7.3% electrolyte-imbalance, and remaining 8.8% pDDIs were unknown in nature. CONCLUSIONS: Based on the study findings, it is concluded that the incidence of pDDIs is ninety percent in renal impairment patients. The majority of pDDIs are pharmacokinetic in nature and significant in severity. Therefore, the pDDIs should be assessed carefully at the time of drug prescribing to prevent over or underestimation of pDDIs and pDDIs associated adverse outcomes.