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Background: A new cardiopulmonary resuscitation technique, chest compressions with sustained inflation (CC + SI) might be an alternative to both the neonatal [3:1compressions to ventilations (3:1C:V)] and paediatric [chest compression with asynchronous ventilation (CCaV)] approaches. The human factors associated with this technique are unknown. We aimed to compare the physical, cognitive, and team-based human factors for CC + SI to standard CPR (3:1C:V or CCaV). Methods: Randomized crossover simulation study including 40 participants on 20 two-person teams. Workload [National Aeronautics and Space Administration Task Load Index (NASA-TLX)], crisis resource management skills (CRM) [Ottawa Global Rating Scale (OGRS)], and debrief analysis were compared. Results: There was no difference in paired NASA-TLX scores for any dimension between the CC + SI and standard, adjusting for CPR order. There was no difference in CRM scores for CC + SI compared to standard. Participants were less familiar with CC + SI although many found it simpler to perform, better for transitions/switching roles, and better for communication. Conclusions: The human factors are no more physically or cognitively demanding with CC + SI compared to standard CPR (NASA-TLX and participant debrief) and team performance was no different with CC + SI compared to standard CPR (OGRS score).