OBJECTIVES Drug-drug interaction is a common error in poly-medication and contributes a major part in adverse drug reactions.  The aim of the present study was to evaluate the percentage of potential drug-drug interactions in the prescription in the region of South Punjab Pakistan prescribed by the medical practitioner METHODS A total of 100 prescriptions were included in this study. Institution based retrospective study was performed in Nishter Hospital Multan, Pakistan, the 3rd oldest medical institution of Pakistan, which has a capacity of 1800 beds and having a best facility to hold a large number of emergencies at a time.   Prescriptions were collected to see the Drug - Drug interactions and compared with the standard reference of important DDI’s. The potential drug-drug interactions were categorized according to their severity, effect and mechanism.  RESULTS  the study showed that among 100 prescriptions (543 medicines),   41% of prescriptions have potential DDI’s. Mostly prescribed drugs were the antibiotics (38%), and the drugs belonging to class analgesic were found to contribute mostly in drug-drug interactions (26.50%). The survey showed the total of 71 interactions and their severity level accounting as major (20.10%), moderate (63.4%) and minor (15.90). The mechanism by which the drugs interact with one another showed that there were pharmacokinetic (60.5%), pharmacodynamic (38.6%) and few of them interact by the mechanism which was not specified in the available literature (0.9%).  CONCLUSIONS: Drug-drug interactions occur in poly-medication and need to be evaluated and monitored for the positive impact on the medication use system and improvement of quality of patient care. A clinical pharmacist with its accurate knowledge of drug, their effect on human organs and their interaction with other can monitor and manage these drug interactions.