Background: Researchers and research funders often have reason to identify and prioritise research questions. Lomas’ framework (Milbank, 2003) for priority-setting includes identifying stakeholders, assembling data, consultation and validation of priority issues, and translation and validation of primary research themes. We have built on this framework to develop a method of systematically appraising existing literature in a broad topic area, and prioritising research areas for Cochrane reviews or for new primary studies. Objectives: We developed methods of identifying and prioritising research questions in the broad clinical areas of Traumatic Brain Injury (TBI) and Spinal Cord Injury (SCI) for the Victorian Neurotrauma Initiative (Australia). This systematic approach for prioritising research questions has helped us to map the research landscape and identify and prioritise evidence gaps in TBI and SCI. Methods: At an evidence mapping workshop key clinical questions in the prehospital care of TBI and SCI. Fourteen stakeholders participated. A Nominal Group Technique was employed to brainstorm interventions, outcomes, context, and patient factors. Research questions were then developed and prioritised using a questionnaire that asked participants to rank each of the identified questions in terms of clinical importance, novelty and controversy surrounding the topic. Results: The mapping workshop identified 29 key questions for prehospital care in TBI and SCI. Eleven were identified as high-priority (eight for TBI and three for SCI) from the questionnaire. A number of clinical questions were identified for which no primary studies were found in the literature. Conclusions: This method (incorporating both qualitative and quantitative techniques) is a simple and effective practice for generating and prioritising research questions in broad clinical areas. It may be applicable to a number of different settings.