IntroductionOut-of-hospital cardiac arrest (OHCA) has a high global incidence and mortality rate, with early defibrillation significantly improving survival. Our aim was to assess the feasibility of autonomous drone delivery of automated external defibrillators (AED) in a non-urban area with physical barriers and compare the time to defibrillate (TTD) with bystander retrieval from a public access defibrillator (PAD) point and helicopter emergency medical services (HEMS) physician performed defibrillation. MethodsThis randomized simulation-based trial with a cross-over design included bystanders performing AED retrievals either delivered by automated drone flight or on foot from a PAD point, and simulated HEMS interventions. The primary outcome was the time to defibrillation, with secondary outcomes comparing workload, perceived physical effort, and ease of use. ResultsThirty-six simulations were performed. Drone-delivered AED intervention had a significantly shorter TTD [2.2 (95 % CI 2.0–2.3) min] compared to PAD retrieval [12.4 (95 % CI 10.4–14.4) min] and HEMS [18.2 (95 % CI 17.1–19.2) min].The self-reported physical effort on a visual analogue scale for drone-delivered AED was significantly lower versus PAD [2.5 (1 – 22) mm vs. 81 (65–99) mm, p = 0.02]. The overall mean workload measured by NASA-TLX was also significantly lower for drone delivery compared to PAD [4.3 (1.2–11.7) vs. 11.9 (5.5–14.5), p = 0.018]. ConclusionThe use of drones for automated AED delivery in a non-urban area with physical barriers is feasible and leads to a shorter time to defibrillation. Drone-delivered AEDs also involve a lower workload and perceived physical effort than AED retrieval on foot.