BACKGROUND: Direct oral anticoagulants (DOACs) are widely used as first-line agents in various clinical settings. However, there is very little evidence regarding their use in critically ill patients in the intensive care unit (ICU), given the gap in the literature regarding their safety in this population and the concerns of bleeding and alterations in pharmacokinetics. Therefore, this study aimed to evaluate the prescribing pattern and safety of DOAC use in critically ill patients. METHODS: This was a single-centre retrospective chart review study involving critically ill patients with confirmed prehospital use of DOACs who either continued their use of DOACs or switched to a therapeutic parenteral anticoagulant agent (enoxaparin or heparin) during the admission to the medical ICU and/or coronary care unit (CCU). The primary outcome was the incidence of major bleeding (MB) events. The secondary outcomes included the incidence of new thrombosis and medical ICU/CCU mortality and hospital and medical ICU/CCU lengths of stay (LOS). RESULTS: A total of 675 patients were screened for inclusion. A total of 302 patients were included in the final analysis, with 167 patients in the DOAC group and 135 patients in the parenteral anticoagulant group. There were no differences between the groups in terms of the incidence of MB (11% vs. 9%, p = 0.61) or new thrombosis (1% vs. 3%, p = 0.50). The overall medical ICU/CCU mortality rate was lower in the DOAC group compared to the parenteral anticoagulant group (7% vs. 15%, p = 0.03). Additionally, the DOAC group had shorter medical ICU/CCU stays (6 days [4-11] vs. 11 days [5-24], p <
0.001) and shorter hospital stays (7 days [5-13] vs. 13 days [7-35], p <
0.001), respectively. CONCLUSION: Compared with the use of parenteral anticoagulants, the use of DOACs in critically ill patients was associated with a similar incidence of MB and new thrombotic events. The observed differences in mortality and LOS between the groups may be attributed to variability in physician decision-making regarding anticoagulation strategies, potentially influenced by patient-specific factors and severity of illness. Further prospective studies to determine the optimal anticoagulation strategy in critically ill patients are warranted.