Background: Having to work in unpredictable and critical conditions, emergency care services (EMS) personnel experience complicated situations at the scene of accidents which, inevitably, influence their clinical decisions. There is a lack of research into the challenges which these professionals encounter. Accordingly, the present study aims to explore the major challenges and barriers which affect clinical decision-making from the perspective of EMS personnel. Methods: The present study is a qualitative work with a content analysis approach. Selected via purposeful sampling, the subjects were 25 members of the EMC personnel in Iran who met the inclusion criteria. The study lasted from December 2019 to July 2020. Sampling was maintained to the point of data saturation. Data were collected using semi-structured, in-depth, individual interviews. The collected data were analyzed via qualitative content analysis. Results: 4 main categories—professional capabilities, occupational and environmental factors, inefficient organizational management, and ethical issues—and 23 subcategories were extracted from the findings of the study. Conclusion: The results of the present study show that personal and occupational factors, organizational management, and ethical issues are the most significant sources of challenge which affect the clinical decision-making and, consequently, the performance of EMC personnel at the scene of accidents. Thus, it is essential that pre-hospital emergency care managers improve the quality of EMC personnel’s clinical decision-making skills and the reliability of care provided by them by creating the right professional and organizational settings, free of occupational distress.