Background: There is uncertainty about the optimal approach to screen for clinically important cervical spine (C-spine) injury following blunt trauma. We conducted a systematic review to investigate the diagnostic accuracy of the Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria, 2 rules that are available to assist emergency physicians to assess the need for cervical spine imaging. Methods: We identified studies by an electronic search of CINAHL, Embase and MEDLINE. We included articles that reported on a cohort of patients who experienced blunt trauma and for whom clinically important cervical spine injury detectable by diagnostic imaging was the differential diagnosis; evaluated the diagnostic accuracy of the Canadian C-spine rule or NEXUS or both; and used an adequate reference standard. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies criteria. We used the extracted data to calculate sensitivity, specificity, likelihood ratios and post-test probabilities. Results: We included 15 studies of modest methodologic quality. For the Canadian Cspine rule, sensitivity ranged from 0.90 to 1.00 and specificity ranged from 0.01 to 0.77. For NEXUS, sensitivity ranged from 0.83 to 1.00 and specificity ranged from 0.02 to 0.46. One study directly compared the accuracy of these 2 rules using the same cohort and found that the Canadian C-spine rule had better accuracy. For both rules, a negative test was more informative for reducing the probability of a clinically important cervical spine injury. Interpretation: Based on studies with modest methodologic quality and only one direct comparison, we found that the Canadian C-spine rule appears to have better diagnostic accuracy than the NEXUS criteria. Future studies need to follow rigorous methodologic procedures to ensure that the findings are as free of bias as possible.