Background: A drug interaction occurs when the effect of a drug is altered by other drugs; it may affect the drug's pharmacokinetics or pharmacodynamics. In pharmacokinetic type of drug interactions, a drug alters the absorption of another drug or the, distribution, metabolism, or elimination of another drug; in pharmacodynamics type of interactions, the action of a drug is altered by other drugs. This study was conducted to investigate the prevalence of potential drug-drug interaction, to examine the number of drugs used and prevalence of polypharmacy, to determine the frequency, severity and the drug combinations involved in DDIs occurring in ICU. Materials and Methods: This is an observational study carried out at an ICU of a multi-specialty hospital. Patient of age group between 18-80 years of both the gender admitted for more than 24 hours and prescribed at least more than 2 drugs are included in the study. All the relevant and necessary details of the patients including the demographic data, laboratory parameters and drug therapy details were collected from the patient case notes. The patient drug therapy were reviewed every day and assessed for any drug-drug interactions. Results: A total of 151 prescriptions were assessed out of which 82 were male and 69 were female. In the study group the average age was 54.6 and association was found between the DI and increased age. There were around 1,709 drugs prescribed and average drugs per prescription was 11.2. From a total of 276 drug interactions found, 46 drug interactions were of major severity, 184 drug interactions of moderate severity and 46 drug interactions of minor severity. Mechanism of DDI was identified of which 85(30.7%) DDI showed pharmacokinetic mechanism, 135(48.9%) DDI showed pharmacodynamic mechanism and 57(20.6%) DDI showed unknown mechanism. The prevalence of drug-drug interaction was seen more in age group of 41-60 years. Conclusion: Prevalence of potential DDIs is high in intensive care units and is predisposed by factors such as a number of drugs received by patients, comorbid conditions; complex pharmacotherapies administered and geriatrics. Health professionals who provide care to these patients should be aware to identify and prevent possible drug events. Also, the pharmacist's involvement might have allowed greater familiarity of physicians regarding clinically relevant drug-drug interactions, optimizing the quality of the prescriptions, especially in critical care units. Therefore,