Drug-drug interactions (DDIs) with serious adverse consequences for patients at intensive care unit (ICU) occur with the prevalence of 5.3%. The aim of our study was to reveal the risk factors for potential DDIs among the ICU patients. This retrospective cohort analysis took place in the ICU of the Clinical Center Podgorica, Montenegro, between June 1, 2017 and September 30, 2018. The study was conducted as a chart review of the ICU patients (n = 99) who spent ≥ 2 days in the ICU. The main outcome measure was the number of DDIs per patient. Ninety-four percent of patients had at least one potential DDI, while 20% of patients had at least one potential DDI which required a change of therapy. The number of potential DDIs per patient according to the Medscape was 6.6 ± 9.1 and 3.8 ± 4.9 according to the Epocrates. A higher number of drugs (or therapeutic groups) prescribed per patient increased the number of potential DDIs, including those which required a change of therapy. The patients who were prescribed antiarrhythmics, anticoagulants or two antiplatelet drugs experienced more DDIs than patients without these therapeutic groups, while delirium, dementia and drug allergy were protective factors. The main limitation of our study was its uni-centerdness, which allowed for certain degree of bias. Routine screening of the ICU patients with high number of prescribed drugs who receive antiarrhythmics, anticoagulants or double antiplatelet therapy for potential DDIs may prevent a great deal of DDIs with potentially deleterious effects.