BackgroundAdvances in vertical take-off and landing (VTOL) technologies may enable drone-like crewed air ambulances to rapidly respond to out-of-hospital cardiac arrest (OHCA) in urban areas. We estimated the impact of incorporating VTOL air ambulances on OHCA response intervals in two large urban centres in France and Canada. MethodsWe included adult OHCAs occurring between Jan. 2017–Dec. 2018 within Greater Paris in France and Metro Vancouver in Canada. Both regions utilize tiered OHCA response with basic (BLS)- and advanced life support (ALS)-capable units. We simulated incorporating 1–2 ALS-capable VTOL air ambulances dedicated to OHCA response in each study region, and computed time intervals from call reception by emergency medical services (EMS) to arrival of the: (1) first ALS unit (“call-to-ALS arrival interval”); and (2) first EMS unit (“call-to-first EMS arrival interval”). ResultsThere were 6,217 OHCAs included during the study period (3,760 in Greater Paris and 2,457 in Metro Vancouver). Historical median call-to-ALS arrival intervals were 21 min [IQR 16–29] in Greater Paris and 12 min [IQR 9–17] in Metro Vancouver, while median call-to-first EMS arrival intervals were 11 min [IQR 8–14] and 7 min [IQR 5–8] respectively. Incorporating 1–2 VTOL air ambulances improved median call-to-ALS arrival intervals to 7–9 min and call-to-first EMS arrival intervals to 6–8 min in both study regions (all P < 0.001). ConclusionVTOL air ambulances dedicated to OHCA response may improve EMS response intervals, with substantial improvements in ALS response metrics.