AIM: To assess the feasibility and safety of drone-delivered automated external defibrillators (AEDs) in real out-of-hospital cardiac arrests (OHCAs) in Denmark, addressing the critical need for timely defibrillation in OHCAs. METHODS: In this prospective clinical study in Aalborg, Denmark, an AED-carrying drone was dispatched for suspected OHCAs, from June 2022 to April 2023. The drone was stationed in an urban area (maximum flight-radius 6 km, covering 110,000 inhabitants) within designated airspace not requiring preflight approval from air-traffic control. Upon OHCA-suspicion, the emergency medical dispatcher activated the drone, which autonomously took off and flew beyond-visual-line-of-sight to the OHCA-location. On-site, a remote drone pilot (stationed cross-border) winched down the AED near the patient's location. Flights were restricted to dry weather, mean windspeeds <
8 m/s, and 8 am to 10 pm. RESULTS: Of 76 suspected OHCAs, 27 occurred during non-operating hours (nighttime). Of the remaining 49 OHCAs, 16 (33%) were eligible for drone take-off, all of which resulted in successful AED-delivery, without any adverse events. Weather caused 14 cancellations (29%), technical issues (dispatch centre, drone, or hangar problems) 13 (27%), and closed airspace 6 (12%). The median drone response time from activation to AED-delivery was 04:47 minutes (IQR 03:45 - 05:27), and the corresponding ambulance response time was 03:25 minutes (IQR 02:43 - 04:14). No drone-delivered AEDs were attached. CONCLUSION: This study demonstrates the safety and feasibility of drone-delivered AEDs to real OHCAs. Improved time to AED delivery was limited due to swift ambulance service, highlighting the importance of strategic AED drone placement.