Introduction: Utilization of CT imaging has risen dramatically with increases in availability, but without corresponding improvements in patient outcomes for many clinical scenarios. Previous attempts to improve imaging appropriateness have met with limited success, with commonly cited barriers including a lack of confidence in patient outcomes, medicolegal risk, and patient expectations. The objective of this study was to assess the impact of an electronic clinical decision support (CDS) intervention to reduce CT utilization for emergency department (ED) patients with mild traumatic brain injury (MTBI). Methods: This was a cluster-randomized, controlled trial with physicians as the unit of randomization. All emergency physicians (EPs) at 4 urban adult EDs and 1 urgent care center were randomly assigned to receive evidence-based imaging CDS (intervention) or no CDS (control) for patients with MTBI over a 1-year study period. CDS was launched in an external web browser whenever an intervention EP ordered a non-enhanced head CT from the computerized physician order entry (CPOE) system for ED patients CTAS 2-5 with a CEDIS chief complaint of head injury; however, interaction with CDS was voluntary. The CDS tool provided detailed information to physicians about the Canadian CT Head Rule, including patient eligibility, exclusion criteria, risk factors and probability of serious injury, as well as an imaging recommendation (yes/no). CDS recommendations could be printed for the medical record as could educational patient handouts to support physician decision making. The primary outcome was CT utilization for patients with MTBI on the index visit. Secondary outcomes included ED length of stay (LOS), and return visits, CT use, hospital admission and traumatic head injury diagnoses over the next 30-days. This study was REB approved. Results: Physician demographics and baseline CT utilization for MTBI patients were similar among intervention and control EPs during a 2-year pre-intervention period. In the first 8-months following CDS implementation, 102 intervention EPs saw 2,189 eligible patients while 100 control EPs saw 1,707 patients. Intervention EPs voluntarily interacted with CDS on 36.2% of eligible encounters. Head CT utilization was lower among intervention EPs than controls (38.5% vs 45.1%, p<0.0001) as was ED LOS (201 vs 218.5 minutes, p<0.001). There was no difference in 30-day ED return visits, head CT utilization, hospital admission or traumatic head injury diagnoses. Conclusion: In one of the largest RCTs of CDS to date, exposure to CDS was associated with decreased head CT utilization and shorter LOS on the index visit, and no difference in 30-day head CT use, return ED visits or hospital admission. These results suggest that a comprehensive CDS implementation may be able to overcome several barriers to use of decision rules and may contribute to improved clinical decision making and decreased CT utilization.