Purpose: The purpose of this study was to investigate the cause of acute fatal poisoning and the time of death by analyzing the National Emergency Department Information System (NEDIS) of South Korea. Methods: The NEDIS data from 2014 to 2018 excluding non-medical visits were used for this study. The patients with acute poisoning were extracted using diagnostic codes. The toxic substances were classified into pharmaceuticals, pesticides, gases, artificial poisonous substances, and natural toxic substances. Patients were classified according to the time of death, place of death, and region. In each case, the most causative substances of poisoning were identified. Results: There were 380,531 patients including poisoning-related diagnoses, of which 4,148 (1.1%) died, and the WHO age-standardized mortality rate was 4.8 per 100,000. Analysis of 2,702 death patients whose primary diagnosis was acute poisoning, the most common cause of poisoning death was pesticides (62%), followed by therapeutic drugs, gas, and artificial toxic substances. Herbicides were the most common pesticides at 64.5%. The proportion of mortality by time, hyperacute (<6 h) 27.9%, acute (6-24 h) 32.6%, subacute (1-7 d) 29.7%, and delayed period (>7 d) were 9.8%. Conclusion This study suggests that the most common cause of poisoning death was pesticides, and 60% of deaths occurred within 24 hours. The 71% of mortality from pesticides occurred within 6-24 hours, but mortality from gas was mostly within 6 hours. According to the geographic region, the primary cause of poisoning death was varied to pesticides or pharmaceuticals.