Background: Organ donation following brain death has become an important way of supplying organs for transplantation in many countries. This practice is less common in Iran for different reasons. Therefore, this study aims to explore the obstacles to organ donation following brain death in Iran. Methods: This qualitative research was conducted following the conventional content analysis method. The study population consisted of individuals with a history of brain death among their blood relatives who refused to donate the organs. Snowball sampling was employed to select the participants. In-depth semi-structured interviews were conducted for data gathering. Theoretical saturation was achieved through 20 interviews. Data analysis was done following the steps proposed by Graneheim and Lundman. Lincoln and Guba's criteria were used to ensure data rigor and transferability of the study. Results: Data analyses revealed 185 codes, 23 categories, and seven themes including, poor knowledge about brain death and organ transplantation from a dead body, cultural beliefs, religious beliefs, deficiencies of requesting process, fear and concerns, inability to make a decision, and social learning. Conclusion: There were several factors in families' reluctance to donate organs of a brain-dead patient. Through improving knowledge and changing cultural beliefs in society, it is possible to take large steps towards promoting organ donation from brain-dead patients.