Background:The emergency department is the entrance gate of patients to a hospital. Hospitals are confronted with major challenges in radiation, nuclear accidents, and nuclear terrorism. Iran is also at risk of disasters, accidents, and threats, so, the possibility of nuclear and radiation accidents cannot be neglected. Objectives: The present study aimed to extract the effective factors in emergency department preparedness of hospitals for radiation, nuclear accidents, and nuclear terrorism in Iran. Methods: This qualitative study was conducted using in-depth semi-structured interviews with 32 key informants selected through purposive and snowball sampling. Experts were from seven different specialties. Data were analyzed using the thematic analysis method in order to extract the effective factors in emergency department preparedness of hospitals for radiation, nuclear accidents, and nuclear terrorism in Iran in 2019. The interviews were held in the cities of Bushehr, Tehran, Shiraz, and Isfahan from September 2018 to February 2019. Results: Effective factors in emergency department preparedness of hospitals were categorized into staff preparedness, equipment preparedness, and system preparedness with 20 subcategories. The experts emphasized that training courses and exercises could enhance the preparedness and response to these accidents. Conclusions: This study showed that the emergency departments of hospitals in Iran have many challenges. When the country moves towards having nuclear technology, must also provide the infrastructure of the preparedness. There must be an attempt to reduce these challenges by providing financial and structural support. Identifying effective factors in preparation can be helpful in setting up programs for emergency department preparedness of hospitals against nuclear and radiation accidents.