Contrast-enhanced whole-body computed tomography (also called "pan-scanning") is considered to be a conclusive diagnostic tool for major trauma. We sought to determine the accuracy of this method, focusing on the reliability of negative results. Between July 2006 and December 2008, a total of 982 patients with suspected severe injuries underwent single-pass pan-scanning at a metropolitan trauma centre. The findings of the scan were independently evaluated by two reviewers who analyzed the injuries to five body regions and compared the results to a synopsis of hospital charts, subsequent imaging and interventional procedures. We calculated the sensitivity and specificity of the pan-scan for each body region, and we assessed the residual risk of missed injuries that required surgery or critical care. A total of 1756 injuries were detected in the 982 patients scanned. Of these, 360 patients had an Injury Severity Score greater than 15. The median length of follow-up was 39 (interquartile range 7-490) days, and 474 patients underwent a definitive reference test. The sensitivity of the initial pan-scan was 84.6% for head and neck injuries, 79.6% for facial injuries, 86.7% for thoracic injuries, 85.7% for abdominal injuries and 86.2% for pelvic injuries. Specificity was 98.9% for head and neck injuries, 99.1% for facial injuries, 98.9% for thoracic injuries, 97.5% for abdominal injuries and 99.8% for pelvic injuries. In total, 62 patients had 70 missed injuries, indicating a residual risk of 6.3% (95% confidence interval 4.9%-8.0%). We found that the positive results of trauma pan-scans are conclusive but negative results require subsequent confirmation. The pan-scan algorithms reduce, but do not eliminate, the risk of missed injuries, and they should not replace close monitoring and clinical follow-up of patients with major trauma.