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Background: Cognitive aids (CAs) are clinical tools guiding clinical decision-making during critical events in the operating room. They may counteract the adverse effects of stress on the non-technical skills of the attending clinician(s). Although most clinicians acknowledge the importance of CAs, their uptake in clinical practice seems to be lagging behind. This situation has led us to investigate which features of CAs may enhance their uptake. Therefore, in this systematic review we explored the optimums regarding the 1) timing to consult the CA, 2) person consulting the CA, 3) location of the CA in the operating room, 4) CA design (paper vs. electronic), 5) CA lay-out, 6) reader of the CA and 7) if the use of CAs in the form of decision support tools lead to improved outcome. Methods: Seven PICO-questions guided our literature search in 4 biomedical databases (MEDLINE, Embase, Web of Science and Google Scholar). We selected English-language randomized controlled trials (RCTs), observational studies and expert opinions discussing the use of cognitive aids during life-threatening events in the operating theatre. Articles discussing non-urgent or non-operating room settings were excluded. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We found 7 RCTs, 14 observational studies and 6 expert opinions. All trials were conducted in a simulation environment. The person who should trigger the use of a cognitive aid and the optimal timing of its initiation, could not be defined by the current literature. The ideal location of the cognitive aids remains also unclear. A favorable lay-out of an aid should be well-structured, standardized and easily readable. In addition, several potentially beneficial design features are described. RCT’s could not demonstrate a possible superiority of either electronic or paper-based aids. Both have their advantages and disadvantages. Furthermore, electronic decision support tools are potentially associated with an enhanced performance of the clinician. Likewise, the presence of a reader was associated with an improved performance of key steps in the management of a critical event. However, it remains unclear who should fulfill this role. Conclusion: Several features of the design or utilization of CAs may play a role in enhancing the uptake of CAs in clinical practice during the management of a critical event in the operating room. However, robust evidence supporting the use of a certain feature over another is lacking.