Purpose: The aim of this study was to determine the drug-drug interactions that are frequently encountered in critically ill patients and the factors that predict these interactions. Materials and Methods: All patients who were admitted to the pediatric intensive care unit (13 bed) of a university hospital and used more than one drug in their treatment were included in this prospective and cross-sectional study. Patients' demographics, laboratory findings, and medications included in their treatment were evaluated daily by a clinical pharmacist. The UpToDate® database was used to detect potential drug interactions. Results: During the study, 797 potential drug-drug interactions were detected in 55 (83.33%) of 66 patients followed. All these interactions were evaluated by the clinical pharmacist and 114 recommendations were made to the physicians following the treatment regarding these potential interactions. Eighty-five (74.56%) of these recommendations were accepted by physicians. Within the scope of the study, each patient was followed up for a median of 9 (2-63) days, and the median value of potential drug interactions detected during this period was calculated as 7 (1-89). Conclusion: The existence of pDDIs was significantly associated with the number of prescribed medications. Exposure to pDDIs is frequent in critically ill pediatric patients and related to the number of medications. Daily and close cooperation between clinicians and clinical pharmacists is recommended to prevent harmful outcomes of DDIs. In order to minimize this risk, it is recommended to avoid polypharmacy as much as possible and to offer alternatives to inducer and inhibitor drugs in treatment.