Introduction Globally, very few settings have undertaken prehospital randomized controlled trials. Given this lack of experience, there is a risk that such trials in these settings may result in protocol deviations, increased prehospital intervals, and increased cognitive load, leading to error. Ultimately, this may affect patient safety and mortality. The aim of this study was to assess the effect of trial-related procedures on simulated scene interval, self-reported cognitive load, medical errors, and time to action. Methods This was a prospective simulation study. Using a cross-over design, ten teams of prehospital clinicians were allocated to three separate simulation arms in a random order. Simulations were: (1) Eligibility assessment and administration of freeze-dried plasma (FDP) and a hemoglobin-based oxygen carrier (HBOC), (2) Eligibility assessment and administration of HBOC, (3) Eligibility assessment and standard care. All simulations also required clinical management of hemorrhagic shock. Simulated scene interval, error rates, cognitive load (measured by NASA Task Load Index), and competency in clinical care (assessed using the Simulation Assessment Tool Limiting Assessment Bias (SATLAB)) were measured. Mean differences between simulations with and without trial-related procedures were sought using one-way ANOVA or Kruskal-Wallis test. A p-value of <0.05 within the 95% confidence interval was considered significant. Results Thirty simulations were undertaken, representing our powered sample size. The mean scene intervals were 00:16:56 for Simulation 1 (FDP and HBOC), 00:17:22 for Simulation 2 (HBOC only), and 00:14:24 for Simulation 3 (standard care). Scene interval did not differ between the groups (p = 0.27). There were also no significant differences in error rates (p = 0.28) or cognitive load (p = 0.67) between the simulation groups. There was no correlation between cognitive load and error rates (r = 0.15, p = 0.42). Competency was achieved in all the assessment criteria for all simulation groups. Conclusion In a simulated environment, eligibility screening, performance of trial-related procedures, and clinical management of patients with hemorrhagic shock can be completed competently by prehospital advanced life support clinicians without delaying transport or emergency care. Future prehospital clinical trials may use a similar approach to help ensure graded and cautious implementation of clinical trial procedures into prehospital emergency care systems.