The purpose of this study was to detect the incidence of potential drug-drug interactions (DDI) in renal failure patients in Khartoum state, Sudan. It is important to consider the problem of polypharmacy and drug interactions in patients with renal failure, including drug- drug, drug- herb and drug- food interactions. This was cross sectional study covered selected renal failure centres in Khartoum state, Sudan, during 2012. The total number of hospitals was eight hospitals. DDIs were determined by using an online drug interaction checker. The main concern of this study was drug-drug interaction of prescribed medication, which accounted about 5.6% major, 61.6% moderate and 28.8% minor. While the interaction of nonprescribed with prescribed drugs; accounted about 0.8% major, 11.2% moderate and 2.4% minor. This study showed that 44.0% of patients used herbal and traditional medicines. In conclusion; Interactions between (prescribed and non-prescribed) drugs occurred and varied from major, moderate and minor. This study also included the incidence of the usage of herbs and traditional medicine concomitantly with prescribed and non- prescribed medications, as most patients believe it might treat renal failure. But it might lead to herb drug interactions and nephrotoxicity in healthy kidneys, which is an issue of concern that may need further studies.