Delivery of automatic electrical defibrillator (AED) by unmanned aerial vehicle (UAV) was suggested for out-of-hospital cardiac arrest (OHCA). The goal of this study is to assess the effect of topographic and weather conditions on call to AED attach time by UAV-AED. We included OHCA patients from 2013 to 2016 in Seoul, South Korea. We developed a UAV-AED flight simulator using topographic information of Seoul for Euclidean and topographic flight pathway including vertical flight to overcome high-rise structures. We used 4 kinds of UAV flight scenarios according to weather conditions or visibility. Primary outcome was emergency medical service (EMS) call to AED attach time. Secondary outcome was pre-arrival rate of UAV-AED before current EMS based AED delivery. Call to AED attach time in topographic pathway was 7.0 min in flight and control advanced UAV and 8.0 min in basic UAV model. Pre-arrival rate in Euclidean pathway was 38.0% and 16.3% for flight and control advanced UAV and basic UAV. Pre-arrival rate in the topographic pathway was 27.0% and 11.7%, respectively. UAV-AED topographic flight took longer call to AED attach time than Euclidean pathway. Pre-arrival rate of flight and control advanced UAV was decreased in topographic flight pathway compared to Euclidean pathway.