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An optimal position of the patient during operation may require a compromise between the best position for surgical access and the position a patient and his or her tissues can tolerate without sustaining injury. This scoping review analysed the existing, contemporary evidence regarding surgical positioning-related tissue damage risks, from both biomechanical and clinical perspectives, focusing on the challenges in preventing tissue damage in the constraining operating room environment, which does not allow repositioning and limits the use of dynamic or thick and soft support surfaces. Deep and multidisciplinary aetiological understanding is required for effective prevention of intraoperatively acquired tissue damage, primarily including pressure ulcers (injuries) and neural injuries. Lack of such understanding typically leads to misconceptions and increased risk to patients. This article therefore provides a comprehensive aetiological description concerning the types of potential tissue damage, vulnerable anatomical locations, the risk factors specific to the operative setting (eg, the effects of anaesthetics and instruments), the complex interactions between the tissue damage risk and the pathophysiology of the surgery itself (eg, the inflammatory response to the surgical incisions), risk assessments for surgical patients and their limitations, and available (including emerging) technologies for positioning. The present multidisciplinary and integrated approach, which holistically joins the bioengineering and clinical perspectives, is unique to this work and has not been taken before. Close collaboration between bioengineers and clinicians, such as demonstrated here, is required to revisit the design of operating tables, support surfaces for surgery, surgical instruments for patient stabilisation, and for surgical access. Each type of equipment and its combined use should be evaluated and improved where needed with regard to the two major threats to tissue health in the operative setting: pressure ulcers and neural damage.