Objective: to identify the factors associated to Potential Drug Interactions with High Alert Medications in the Intensive Care Unit of a Sentinel Hospital. Methods: a cross-sectional, retrospective study using a quantitative approach carried out at a Sentinel Hospital in Rio de Janeiro. The research was based on the analysis of the prescriptions of patients hospitalized in the Intensive Care Unit of the Hospital, in a period of one year, in order to identify the drug interactions related to high alert medications in these prescriptions. Results: Of the 60 prescriptions analyzed, 244 were selected. In these prescriptions, 846 potential drug interactions related to high alert medications and 33 high alert medications were identified. Of the 112 types of potential drug interactions identified, some were more recurrent: tramadol e ondansetron, midazolam and omeprazole, regular insulin and hydrocortisone, fentanyl and midazolam, and regular insulin and noradrenaline. The variables polypharmacy, length of hospital stay, and some specific medications were associated with drug interactions with high alert medications. Conclusion and Implications for practice: It is important to strengthen strategies to reduce adverse drug events. Therefore, the relevance of studies that investigate the origin of these events is highlighted. Drug interactions can represent medication errors. It’s indispensable to work with strategies to better manage the medication system.