Background Road traffic crashes (RTCs) and its associated injuries are one of the most important public health problems in the world. In Iran, RTCs rank second in terms of mortality. To address this issue, there is a need for research-based interventions. Prioritizing researches using a variety of approaches and frameworks to determine the most effective interventions is a key nodal point in the RTCs' research policy planning cycle. Thus, this study aims to generate and prioritize research questions in the field of RTCs in Iran. Methods By adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 25 prominent Iranian academic leaders having role in setting Iran’s long-term road safety goals, a group of research funders, and policymakers. The experts' proposed research questions were independently scored on a set of criteria: feasibility, impact on health, impact on the economy, capacity building, and equity. Following the prioritization of Research Questions (RQs), they were all classified using the 5 Pillar frameworks. Results In total, 145 Research Questions were systematically scored by experts against five criteria. Iran's top 20 road traffic safety priorities were established. The RQs related to “road safety management” and “road and infrastructure” achieved a high frequency. Conclusions The top 20 research questions in the area of RTCs in Iran were determined by experts. The majority of these RQs were related to “road safety management”. The results of this study may contribute to the optimal use of resources in achieving long-term goals in the prevention and control of road traffic crashes and its related injuries. Considering these RQs as research investment options will improve the current status of Road Traffic Injuries (RTIs) at a national level and further advance toward compliance with international goals. If these research priorities are addressed, and their findings are implemented, we can anticipate a significant reduction in the number of crashes, injuries, and deaths.