Background Major gaps persist in the development, validation, and implementation of clinical decision rules (CDRs) for diagnostic imaging. Objectives The objective of this working group and article was to generate a consensus-based research agenda for the development and implementation of CDRs for diagnostic imaging in the emergency department (ED). Methods The authors followed consensus methodology, as outlined by the journal Academic Emergency Medicine (AEM), combining literature review, electronic surveys, telephonic communications, and a modified nominal group technique. Final discussions occurred in person at the 2015 AEM consensus conference. Results A research agenda was developed, prioritizing the following questions: 1) what are the optimal methods to justify the derivation and validation of diagnostic imaging CDRs, 2) what level of evidence is required before disseminating CDRs for widespread implementation, 3) what defines a successful CDR, 4) how should investigators best compare CDRs to clinical judgment, and 5) what disease states are amenable (and highest priority) to development of CDRs for diagnostic imaging in the ED? Conclusions The concepts discussed herein demonstrate the need for further research on CDR development and implementation regarding diagnostic imaging in the ED. Addressing this research agenda should have direct applicability to patients, clinicians, and health care systems.